Dissertations / Theses: 'Lipoproteins'

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Zago, Vanessa Helena de Souza 1984. "Efeitos do polimorfismo T-786C do gene da óxido nítrico sintase endotelial (eNOS) e/ou da atorvastatina sobre parâmetros do metabolismo lipídico em adultos assintmáticos." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309030.

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Orientadores: Eliana Cotta de Faria, José Eduardo Tanus dos Santos
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: O óxido nítrico (NO) é produzido no endotélio vascular pela óxido nítrico sintase endotelial (eNOS), enzima regulada negativamente pela presença do polimorfismo T- 786C, levando à disfunção endotelial. A lipoproteína de alta densidade (HDL) têm funções anti-aterogênicas bem estabelecidas, incluindo mecanismos que aumentam a atividade da eNOS. As estatinas são fármacos que possuem, dentre seus efeitos pleiotrópicos, a melhora na função do endotélio e na composição da HDL. Dada a importância tanto da expressão quanto da atividade da eNOS para a função endotelial, bem como dos efeitos pleiotrópicos das estatinas sobre estas duas variáveis, avaliamos os parâmetros bioquímicos e a composição das sub-frações de HDL (HDL2 e HDL3) após uso de placebo e atorvastatina em uma amostra populacional de 30 indivíduos, divididos em dois grupos: 15 indivíduos portadores do polimorfismo T-786C do gene da eNOS (CC) e 15 não portadores (TT). Duzentos indivíduos foram genotipados, e pareamos conforme idade e IMC 15 indivíduos TT e 15 indivíduos CC, que receberam placebo e/ou atorvastatina na dose de 10mg/dia, por 14 dias. Os parâmetros séricos analisados foram determinados através de métodos bioquímicos enzimáticos, radiométricos, nefelométricos e microultracentrifugação. Mediu-se lípides, lipoproteínas, composição das sub-frações da HDL (HDL2 e HDL3), apolipoproteínas, atividade da proteína de transferência de colesteril éster, metabólitos do NO e proteína C reativa. Após o uso da estatina, como esperado, drásticos efeitos redutores foram observados tanto nos lípides, lipoproteínas, apolipoproteínas e de forma independente do polimorfismo, além da redução de ácidos graxos livres nos portadores do genótipo CC. Nas sub-frações a relação lípides/proteínas foi reduzida tanto em HDL2 quanto em HDL3.O aumento da atividade da CETP nos portadores foi corrigido pela estatina e os níveis de ácidos graxos livres reduziram-se de maneira polimorfismo-dependente, em oposição à redução observada do nitrito, que foi polimorfismo-independente. usPCR e Lp(a) não se modificaram. A atorvastatina pode ter atuado sobre o transporte reverso de colesterol através da redução da atividade da lipase hepática e aumento de atividade da PLTP. Foram observadas interações genótipo/tratamento limítrofes para CETP e Lp(a). Estes resultados sugerem que o tratamento com estatinas pode ser relevante na prevenção primária da aterosclerose em portadores do polimorfismo, independentemente de modificações lipídicas séricas. Portanto estes indivíduos se beneficiariam com o uso de estatinas através da modulação da atividade da CETP e redução da concentração de ácidos graxos livres.
Abstract: Nitric oxide (NO) is produced in the vascular endothelium by endothelial nitric oxide synthase (eNOS), an enzyme negatively regulated by the presence of the T-786C polymorphism, leading to endothelial dysfunction. High-density lipoproteins (HDL) have well-established anti-atherogenic functions, for example mechanisms that enhance eNOS activity. Statins are drugs that have pleiotropic effects, such as the improvement in endothelial function and beneficial composition of HDL. Taking into account both the activity of eNOS on endothelial function, and the validity of the pleiotropic effects of statins, we evaluated the biochemical parameters and the composition of subfractions of HDL (HDL2 and HDL3) after use of placebo and atorvastatin at a dose of 10mg/day for 14 days, in a population sample of 30 individuals divided into two genotype groups of the T-786C polymorphism of the eNOS gene: CC (carriers) or TT (non-carriers). Two hundred individuals were genotyped, and the selected groups paired by age and BMI. The serum parameters analyzed were determined using biochemical enzymatic, radiometric, nephelometric and microultracentrifugation methods. We measured lipids, lipoproteins, the composition of sub-fractions of HDL (HDL2 and HDL3), apolipoproteins, activity of cholesteryl ester transfer protein, NO metabolites and hsCRP. After statin, as expected, drastic effects were observed both in lipids, lipoproteins, apolipoproteins, independently of the polymorphism. In HDL sub-fractions the ratio lipid/protein was smaller in both HDL2 and HDL3. CETP activity and free fatty acids were reduced in a polymorphism-dependent manner, and the reduction of nitrite was polymorphism-independent. hsCRP did not change. Atorvastatin may have acted on the reverse cholesterol transport by reducing the activity of hepatic lipase, increased PLTP activity and reducing CETP. There was a genotype/drug interaction effect on CETP and Lp(a). These results suggest that statin treatment may be relevant for primary prevention of atherosclerosis in patients with the polymorphism, irrespective of serum lipid changes. These individuals would benefit from the use of statins because of reduction of CETP activity and free fatty acids.
Mestrado
Ciencias Biomedicas
Mestre em Ciências Médicas

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Kohn, Meifania Monica. "Lipoprotein ontology: a formal representation of Lipoproteins." Thesis, Curtin University, 2013. http://hdl.handle.net/20.500.11937/1827.

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Lipoproteins serve as a mode of transport for the uptake, storage and metabolism of lipids. Dysregulation in lipoprotein metabolism, known as dyslipidaemia, is strongly correlated to various diseases such as cardiovascular disease. Lipoprotein Ontology provides a formal representation of lipoprotein concepts and relationships that can be used to support the intelligent retrieval of information, faciliate collaboration between research groups, and provide the basis for the development of tools for the diagnosis and treatment of dyslipidaemia.

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Parra, Eliane Soler 1981. "Comparação entre a atividade da proteína de transferência de colesterol esterificado e o tamanho da HDL na associação com a aterosclerose carotídea." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313596.

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Orientadores: Andrei Carvalho Sposito, Eliana Cotta de Faria
Texto em português e inglês
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A lipoproteína de alta densidade (HDL) é um complexo heterogêneo e versátil de partículas com variações funcionais resultantes da integração de uma vasta gama de componentes, como apolipoproteínas, receptores, transportadores, enzimas e fosfolípides, com ações indiretas ou diretas sobre o seu metabolismo. Além disso, as concentrações plasmáticas do colesterol da HDL (HDL-C) e seu tamanho representam importantes fatores inversos ao desenvolvimento de doenças cardiovasculares, particularmente em indivíduos em prevenção primária. A proteína de transferência de colesterol esterificado (CETP) desempenha uma função importante no transporte reverso do colesterol (TRC) que é umas das principais funções antiaterogênicas da HDL. No entanto, a atividade da CETP é inversamente associada às concentrações de HDL-C e ao tamanho da partícula. Adicionalmente, HDL grande demonstra ser mais efetiva no efluxo do colesterol, parte integrante do TRC, comparada à partícula de HDL menor. Nesse contexto, o objetivo do estudo foi avaliar, em indivíduos livres de doença aterosclerótica manisfesta, a associação entre o tamanho da HDL e a redução da atividade da CETP induzida geneticamente com a carga aterosclerótica carotídea. Utilizamos para esse fim dois polimorfismos da CETP, TaqIB e I405V, que foram bem caracterizados funcionalmente e encontrados frequentemente na população. Assim, os objetivos desta tese foram: (i) investigar se a presença dos polimorfismos TaqIB e I405V do gene da CETP está associada às concentrações de HDL-C e à aterosclerose carotídea subclínica (n=207); (ii) pesquisar se, além das concentrações de HDL-C, o tamanho da partícula de HDL está associado à aterosclerose subclínica (n=284). Para estes estudos foram determinados os perfis lipídicos, lipoproteícos e apoproteícos, proteína C-reativa (PCR), anticorpos anti-LDL oxidada, atividades das proteínas CETP e de transferência de fosfolípides (PLTP), HDL2 e HDL3 e o diâmetro da HDL. Os polimorfismos TaqIB e I405V da CETP também foram detectados. A espessura da camada íntima-medial da artéria carótida comum (EIMc) foi mensurada por ultrassonografia. Na presença do menor alelo dos polimorfismos TaqIB e I405V da CETP, EIMc correlacionou-se inversamente com atividade da CETP e positivamente com atividade da PLTP e anticorpos anti-LDL oxidada. Na análise multivariada, a presença do menor alelo do polimorfismo TaqIB, mas não do I405V, foi associado a um aumento de 5,1 vezes de risco de maior EIMc. No entanto, a atividade da CETP não diferiu entre os grupos de presença e ausência do menor alelo do polimorfismo TaqIB. Com relação ao tamanho das partículas, HDL maiores foram associadas a menores EIMc e foram melhores indicadores de risco de aterosclerose carotídea subclínica comparadas às concentrações de HDL-C. Em conclusão, o aumento do tamanho da HDL tem associação independente com a carga aterosclerótica e, embora o polimorfismo TaqIB também se associe, sua interação parece ser independente da atividade da CETP
Abstract: High-density lipoproteins ( HDL ) are a group of heterogeneous and complex particles with versatile functional changes resulting from the integration of a wide range of components, such as apolipoproteins, receptors, transporters, enzymes and phospholipids with indirect or direct actions on your metabolism. In addition, plasma concentrations of HDL cholesterol (HDL -C) and its size are inversely related to the development of cardiovascular diseases, particularly in primary prevention in individuals. The cholesterol ester transfer protein (CETP) plays an important role in reverse cholesterol transport (RCT), which is one of the main functions of HDL. However, CETP activity is inversely related to HDL-C and particle size. Additionally, largest HDL particles have demonstrated a higher cholesterol efflux capacity. In this context, the aim of the study was to evaluate, in individuals free of manifest atherosclerotic disease, the association between the size of HDL and CETP activity genetically induced with carotid atherosclerosis burden. We used for this purpose, two polymorphisms of CETP TaqIB and I405V, which have been well characterized functionally and often found in the population. The objectives of this thesis were: (i) to investigate whether the presence of polymorphisms I405V and TaqIB of CETP gene is associated with HDL-C and subclinical carotid atherosclerosis (n= 207); (ii) to investigate if, in addition to HDL-C, the particle size of HDL is associated with atherosclerosis (n= 284). We determined lipid, lipoprotein profiles and apolipoprotein, C-reactive protein (CRP), antibodies against oxidized LDL, CETP and phospholipid transfer protein (PLTP) activities, HDL2 and HDL3 and HDL size. The TaqIB and I405V CETP polymorphisms were also analyzed. Common carotid artery intima-media thickness (cIMT) was measured using ultrasonography. In the presence of the minor alleles of the TaqIB and I405V polymorphisms of CETP, cIMT was inversely correlated with CETP activity and positively with PLTP activity and antibodies against oxidized LDL. In multivariate analysis, the presence of the minor allele of the TaqIB polymorphism, but not the I405V, was associated with a 5.1 times increased risk of higher cIMT. However, CETP activity did not differ between the presence and absence of minor allele groups of the TaqIB polymorphism. Regarding HDL size, increased HDL size was associated with lower cIMT and was better marker of risk of subclinical carotid atherosclerosis compared to HDL-C. In conclusion, increased size of HDL is independently associated with atherosclerotic and, although TaqIB polymorphism is also associated, its interaction seems to be independent of CETP activity
Doutorado
Clinica Medica
Doutora em Clínica Médica

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González, Muñoz Marta. "Estudi dels canvis en la distribució de les subclasses de lipoproteïnes i partícules romanents en diferents condicions associades a risc arterioscleròtic: més enllà del colesterol." Doctoral thesis, Universitat Rovira i Virgili, 2016. http://hdl.handle.net/10803/401823.

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Tot i els enormes avenços en el camp de la prevenció del risc cardiovascular, una part molt significativa del infarts de miocardi es donen en individus amb un perfil lipídic de rutina normal. L’anàlisi avançat per ressonància magnètica nuclear (RMN) que determina la mida i el número de les partícules lipoproteiques, i la determinació de les lipoproteïnes romanents (LRs), poden donar resposta a les restriccions metodològiques que presenten els paràmetres lipídics convencionals. En aquest context vam plantejar l’estudi en pacients amb Lupus Eritematós Sistèmic (LES), i amb aquest anàlisi avançat donar resposta al seu alt risc arterioscleròtic tot i presentar un perfil lipídic convencional mínimament alterat. Per altra banda, en LES la prevalença d’arteriosclerosi subclínica en edats joves és major que en població general, és a dir que l’edat no té un impacte tant fort en el procés arterioscleròtic. Tant l’edat com l’índex de massa corporal són coneguts i importants factors de risc arterioscleròtic, però mai han estat estudiats des d’aquest punt de vista en una població amb absència de cap patologia crònica. Finalment, donat que el colesterol transportat per la fracció de lipoproteïnes romanents RLP ha estat considerada un factor independent de risc arterioscleròtic, és important conèixer les partícules que la composen. La conclusió és que l’anàlisi avançat de lípids i lipoproteïnes permet veure que la mida i el número de lipoproteïnes, junt amb les LR aporten informació addicional a la obtinguda pels paràmetres lipídics convencionals, en l’efecte del LES, l’edat i l’índex de massa corporal sobre el procés patogènic de l’arteriosclerosi; i el que de manera general anomenem LRs no és un grup homogeni de partícules i caldria deixar de parlar-ne com a tal.
A pesar de los enormes avances en el campo de la prevención del riesgo cardiovascular, una parte muy significativa de infartos de miocardio se dan en individuos con un perfil lipídico de rutina normal. El análisis avanzado por resonancia magnética nuclear (RMN) que determina el tamaño y el número de las partículas lipoproteicas, y la determinación de las lipoproteínas remanentes (LRs), pueden dar respuesta a las restricciones metodológicas que presentan los parámetros lipídicos convencionales. En este contexto planteamos el estudio en pacientes con Lupus Eritematoso Sistémico (LES), y con este análisis avanzado dar respuesta a su alto riesgo aterosclerótico a pesar de presentar un perfil lipídico convencional mínimamente alterado. Por otra parte, en LES la prevalencia de arteriosclerosis subclínica en edades jóvenes es mayor que en población general, es decir que la edad no tiene un impacto tan fuerte en el proceso aterosclerótico. Tanto la edad como el índice de masa corporal son conocidos e importantes factores de riesgo aterosclerótico, pero nunca han sido estudiados desde este punto de vista en una población con ausencia de patología crónica. Por último, dado que el colesterol transportado por la fracción de lipoproteínas remanentes RLP ha sido considerado un factor independiente de riesgo aterosclerótico, es importante conocer las partículas que la componen. La conclusión es que el análisis avanzado de lípidos y lipoproteínas permite ver que el tamaño y el número de lipoproteínas, junto con las LR aportan información adicional a la obtenida por los parámetros lipídicos convencionales, en el efecto del LES, la edad y el índice de masa corporal sobre el proceso patogénico de la arteriosclerosis; y lo que de manera general llamamos LRs no es un grupo homogéneo de partículas y se debería dejar de hablar como tal.
Despite huge advances in the field of cardiovascular risk prevention, a significant proportion of heart attacks occur in individuals with a normal routine lipid profile. Advanced analysis by nuclear magnetic resonance (NMR), which determines the size and number of lipoprotein particles, and the determination of remnant lipoproteins (RLs) can help solve the methodological constraints presented by conventional lipid parameters. In this context we considered the study with advanced analysis, in patients with systemic lupus erythematosus (SLE) to respond to its high-risk atherosclerotic despite presenting a conventional minimally altered lipid profile. Moreover, in LES the prevalence of subclinical atherosclerosis at younger ages is greater than in the general population, meaning that age does not have a strong impact on the atherosclerotic process. Both age and body mass index (BMI) are known and are important risk factors for the atherosclerotic process, but they have never been studied from this point of view, in a population with an absence of any chronic disease. Finally, given that cholesterol transported for the fraction of remnant lipoproteins RLP has been considered an independent risk factor for atherosclerosis, it is important to know the particles composition. The conclusion is that advanced analysis of lipids and lipoproteins allows us to prove that the size and number of lipoproteins, together with LR, provide additional information on the effect of LES, age and BMI, in the pathogenic process of atherosclerosis, from that which is obtained by conventional lipid parameters; and what it is generally called RLs is not an homogeneous group particle and therefore it should not be talked about as such.

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Mallol, Parera Roger. "Development and evaluation of a novel advanced lipoprotein test based on 2d diffusion orderen 1h nmr spectroscopy." Doctoral thesis, Universitat Rovira i Virgili, 2014. http://hdl.handle.net/10803/296439.

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La determinació de la mida i el nombre de lipoproteïnes utilitzant tests avançats de lipoproteïnes és d'un gran interès clínic ja que el nombre de partícules LDL s'ha posicionat com a millor predictor de risc cardiovascular que el colesterol LDL. Tanmateix, els tests avançats de lipoproteïnes actuals encara no s'han introduït en l'àmbit clínic en gran part per la falta d'una estandarització. En aquesta tesi presentem el test LipoScale, un nou test avançat de lipoproteïnes basat en espectroscopia de RMN de difusió 2D. Amb aquest test es pretén obtenir una millor caracterització de les lipoproteïnes plasmàtiques, tant el seu contingut lipídic com la seva mida i nombre de partícules, de manera que amb ell s'aconsegueixi una millor predicció del risc cardiovascular. Durant el desenvolupament del test s’han estudiat diferents patologies i cohorts dins del marc de les malalties metabòliques (les quals són un factor de risc de les malalties cardiovasculars). Entre les malalties estudiades destaquem la diabetis, la dislipèmia aterògena i la síndrome de l’ovari poliquístic (PCOS). A més, també s’han monitoritzat canvis en el perfil de les lipoproteïnes deguts a intervencions nutricionals i a l’exercici. La principal diferència entre la nostra aproximació i la dels mètodes actuals és que aquests últims utilitzen mètodes de RMN 1D estàndards, mentre que el nostre test està basat en l'ús de gradients de camps magnètic, els quals generen espectres 2D amb els que es pot obtenir informació directa i objectiva de la mida de les partícules lipoproteiques. Aquesta tesi ha generat diferents publicacions científiques així com també s'ha fet la sol•licitud d'una patent europea i s'ha creat una spin-off per comercialitzar el test.
La determinación del tamaño y el número de lipoproteínas utilizando tests avanzados de lipoproteínas es de un gran interés clínico ya que el número de partículas LDL se ha posicionado como mejor predictor de riesgo cardiovascular que el colesterol LDL. Sin embargo, los tests avanzados de lipoproteínas actuales aún no se han introducido en el ámbito clínico en gran parte por la falta de una estandarización. En esta tesis presentamos el test LipoScale, un nuevo test avanzado de lipoproteínas basado en espectroscopía de RMN de difusión 2D. Con este test se pretende obtener una mejor caracterización de las lipoproteínas plasmáticas, tanto su contenido lipídico como su tamaño y número de partículas, por lo que con él se consiga una mejor predicción del riesgo cardiovascular. Durante el desarrollo del test se han estudiado diferentes patologías y cohortes dentro del marco de las enfermedades metabólicas (las cuales son un factor de riesgo de las enfermedades cardiovasculares). Entre las enfermedades estudiadas destacamos la diabetes, la dislipemia aterògena y el síndrome del ovario poliquístico (PCOS). Además, también se han monitorizado cambios en el perfil de las lipoproteínas debidos a intervenciones nutricionales y el ejercicio. La principal diferencia entre nuestra aproximación y la de los métodos actuales es que estos últimos utilizan métodos de RMN 1D estándar, mientras que nuestro test está basado en el uso de gradientes de campo magnético, los cuales generan espectros 2D con los que se puede obtener información directa y objetiva del tamaño de las partículas lipoproteicas. Esta tesis a generado diferentes publicaciones científicas así como también se ha hecho la solicitud de una patente europea y se ha creado una spin-off para comercializar el test.
Determination of lipoprotein particle size and particle number using advanced lipoprotein analyses is of particular interest since the LDL particle number has been shown to improve cardiovascular disease risk prediction. Advanced lipoprotein tests (ALT), however, are not yet routinely introduced in clinical practice partly due to the lack of standardization. This thesis presents the LipoScale test, a novel advanced lipoprotein test based on 2D diffusion-ordered 1H NMR spectroscopy. This test is to obtain a better characterization of plasma lipoproteins in terms of their lipid content, particle size and particle number that will allow a better assessment of cardiovascular risk. During the development of the test various diseases and cohorts were studied in the context of metabolic diseases (which are a risk factor for cardiovascular disease). Among the diseases studied we highlight diabetes, atherogenic dyslipidemia and polycystic ovary syndrome (PCOS). In addition, changes were also monitored in the lipoprotein profile due to nutritional interventions and exercise. The main difference between our approach and the current NMR methods is that the latter use standard 1D methods, whereas our test is based on the use of magnetic field gradients, which generate the 2D spectra that can be used to get direct and objective information on lipoprotein particle sizes. This thesis generated various scientific publications, includes an application for a European patent and a spin-off has been created to commercialize the test.

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Soran, Handrean. "Glycation of Lipoproteins and the Role High Density Lipoprotein and Paraoxonase -1." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.532197.

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Bassora, Fernanda Dutra Santiago 1982. "Modulação funcional e genica de lipides e lipoproteinas plasmaticos e da aterosclerose carotidea na hiperalfalipoproteinemia." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309023.

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Orientador: Eliana Cotta de Faria
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Está bem estabelecida na literatura especializada a associação inversa entre as concentrações plasmáticas de colesterol das lipoproteínas de alta densidade (HDL-C) e a incidência de doença arterial coronariana (DAC). Além de propriedades anti-oxidante, anti-inflamatória e anti-trombótica, a HDL participa do transporte reverso de colesterol, via pela qual o colesterol é captado das lipoproteínas e das membranas células periféricas e transportado ao fígado para sua excreção na forma livre ou de ácidos biliares. A lipase hepática (LH) possui função crucial no transporte reverso do colesterol, por sua atividade lipolítica e pela função de ligante à lipoproteínas facilitando sua captação tissular. A proteína de transferência de ésteres de colesterol (CETP), e mesma importância metabólica, promove a troca de ésteres de colesterol por triglicérides entre a HDL e as lipoproteínas ricas em triglicérides. Mutações nos genes que codificam estas proteínas têm sido muito estudadas para se compreender a função destas no metabolismo lipídico. O modelo experimental da hiperalfalipoproteinemia tem sido utilizado no decorrer dos últimos anos com o intuito de elucidar os mecanismos de ação da HDL e das proteínas reguladoras do seu metabolismo. A hiperalfalipoproteinemia é caracterizada pelo aumento das concentrações de HDL-C e é causada principalmente por deficiências genética de CETP e/ou LH. Os objetivos desta dissertação foram o de se estabelecer à modulação da hiperalfalipoproteinemia sobre os parâmetros antropométricos, bioquímicos, moleculares (¿514C/T do gene da LH e I405V do gene da CETP) e radiológicos (espessura da camada íntima média de carótidas) em uma amostra populacional brasileira. O estudo foi conduzido em 291 voluntários de ambos os sexos, classificados como hiperalfalipoproteinemicos (Hiper-A), HDL-C =68mg/dL, ou controles, HDL-C<68 e =32 mg/dL, de acordo com o valor do percentil 90, obtido em um estudo prévio do Laboratório de Lípides a partir população normolipidêmica. Os polimorfismos LH-514C/T e CETP I405V foram identificados através de técnicas de reação em cadeia polimerase (PCR) e a espessura da camada íntima-média de carótidas (EIM) pela ultra-sonografia de alta resolução. Em um primeiro trabalho observou-se em um sub-grupo de 169 indivíduos, com a medida da EIM, que somente a idade foi correlacionada com a EIM na hiperalfalipoproteinemia, enquanto que em controles houve modulação positiva pela idade, sexo masculino, pressão arterial sistólica, e controversamente com relatos da literatura, com HDL-C. Apesar de Hiper-A possuir um perfil com maior número de fatores de risco cardiovasculares, a semelhança encontrada na EIM de carótidas, assim como, da freqüência de EIM maior que 1 mm poderia, em parte, ser explicada pela grande diferença de modulação entre os grupos apontando para um traço protetor contra a aterosclerose carotídea em hiperalfalipoproteinemia. A ateroproteção reduzida em controles, tanto em homens quanto em mulheres, está de acordo com a observada associação negativa neste grupo entre EIM e a CETP com possível presença de HDL com a composição química alterada (ricas em TG e pobres em ésteres de colesterol), e ocorreu possìvelmente no sub-grupo masculino, com perfil pró-aterogênico evidente. Em um segundo trabalho, no sub-grupo de 169 indivíduos, com a medida da EIM, foi avaliado o efeito do polimorfismo LH-514C/T sobre a espessura da camada íntima-média de carótidas na hiperalfalipoproteinemia. Não se observou nenhuma variação de EIM em ambos os grupos em função deste polimorfismo. Quando comparados os grupos, o genótipo CC do polimorfismo LH-514C/T mostrou apenas tendência a maior EIM de carótidas em hiperalfalipoproteinemia (p<0,09), mas a freqüência de EIM maior que 1 mm foi igual. Em um terceiro trabalho, em 282-291 indivíduos foram avaliadas as semelhanças de freqüências entre os polimorfismos LH-514C/T e CETP I405V na hiperalfalipoproteinemia e normolipidemia. Ambos apresentaram altas freqüências, similares entre grupos e entre o polimorfismo LH-514C/T, CC 39%, CT+TT 61%; e o polimorfismo CETP I405V: II 26%, IV+VV 74% e CTL: CC 40%, CT+TT 60%, II 43% e IV+VV 57%. Descrevemos o polimorfismo LH-514C/T na hiperalfalipoproteinemia os TT vs CC apresentaram cintura menor, concentrações mais baixas de colesterol plasmático (C), fosfolípides (FL), LDL-C, estimativa do tamanho da LDL (LDL-C/ApoB). O polimorfismo CETP I405V na hiperalfalipoproteinemia em VV vs II, mostrou alta pressão arterial sangüínea e menores concentrações plasmáticas de HDL2TG e HDL3TG. O genótipo IV teve maiores concentrações plasmáticas de ApoAI e pressão arterial diastólica quando comparado com o genótipo II. Em resumo esta dissertação aponta para efeitos ateroprotetores ou neutros da hiperalfalipoproteinemia em uma amostra de população brasileira sobre a aterosclerose carotídea, inclusive no polimorfismo LH -514C/T. Os polimorfismos LH-514C/T e CETP I405V foram muito semelhantes com relação aos lípides e lipoproteínas séricos, mas não às proteínas reguladoras, oferecendo modulação protetora na hiperalfalipoproteinemia
Abstract: There is an inverse relationship between plasma concentration of high-density lipoprotein (HDL-C) and the risk of coronary arterial disease (CAD). Beyond anti-oxidant, anti-inflammatory and anti-thrombotic properties, HDL plays a role on the reverse cholesterol transport, where cholesterol is taken from lipoproteins and peripheral cells to the liver for excretion. Hepatic lipase (HL) plays a key role in this process, by its lipolitic activities and ligand functions. Cholesterol ester transfer protein (CETP), of equal metabolic importance, facilitates the exchange of cholesterol ester and triglycerides between HDL and triglyceride rich-lipoproteins. Mutations and polymorphisms of these enzymes have being studied in order to evaluate its activity and metabolic consequences. Hyperalphalipoproteinemia (Hyper-A) has being used in the latest years with the purpose of evaluating the anti and pro-atherogenic mechanisms of HDL and of regulating proteins. The aim of this work was to establish the modulation of hyperalphalipoproteinemia in relation to controls on the anthropometric, biochemical, radiological and molecular manifestations. This study was conducted on 291 volunteers, classified as Hyper-A, HDL-C=68mg/dL and controls, HDL-C <68 e 32 mg/dL according to the percentile 90th, obtained from a local normolipidemic population study. We determined clinic data, lipid, lipoproteins and radiological parameters of volunteers. The HL-514C/T and CETP I405V polymorphism were determined by polymerase chain reaction methods. The carotid intima-media thickness measurements were performed high performance ultrasound. We showed in the first manuscript that although possessing a higher risk coronary vascular disease profile the similarity found in carotid could in part be explained by the striking differences in its modulation between the two groups, indicating a protective trait against carotid atherosclerosis in hyperalphalipoproteinemia. In the Hyper-A population, was only correlated with age, while in controls had a positive correlation with age, male sex, systolic blood pressure, and surprisingly with HDL-C. This dissociation between IMT and HDL-C could be accounted for by a small HDL particle number in CTL. In the manuscript 2, the ¿514C/T polymorphism did not contribute to variations in the carotid IMT and Hyper-A did not modulate the IMT variations, contrary to Rundek et al., (2002) who investigated the ¿514C/T polymorphism on variations in the carotid IMT in 87 stroke-free subjects suggested that CC genotypes had increase of carotid IMT, FMT and HALP. The HL-514C/T e CETP I405V polymorphisms, were no associate, were highly prevalent in the two groups but were not associated with HDL-C. In Hyper-A, LH-514C/T induced lower plasma cholesterol (C), phospholipids (PL), LDL-C and LDL size (LDL-C/ApoB). In Hyper-A CETP I405V decreased blood pressure, reduced TG in HDL subfractions 2 and 3 of (HDL2TG and HDL3TG) and increase ApoAI. The HL -514C/T polymorphism in Hyper-A the TT vs CC had lower waist hip-circumference, cholesterol (C) concentrations, phospholipids (PL), LDL-C and estimated size particle by LDL-C/ApoB. The genotype TT was different between 2 groups: in Hyper-A with relation the CTL, had lower HL, estimated size particle by TG/HDL-C and higher HDL2C, HDL3C, HDL3TG, ApoAI and C concentrations and had higher C, estimated size particle by LDL-C/ApoB, ApoAI, HDL2C, HDL3C and estimated size particle by TG/HDL-C. The CETP I405V polymorphism in Hyper-A, the VV vs II had higher Systolic Blood Pressure and lower HDL2TG e HDL3TG concentrations. The IV genotype had higher ApoAI concentration and Diastolic Blood Pressure. In Hyper A, the VV genotype had higher HDL2C, HDL3C, ApoAI, e TG concentrations and reduced concentration of VLDL- and estimated size particle of LDL by TG/HDL-C. In summary, this work indicates an athero-protector and neutral effect on the carotid atherosclerosis in Hyper-A between HL-514C/T and CETP I405V polymorphisms both modulated for plasma lipids more atheroprotective
Mestrado
Ciencias Basicas
Mestre em Clinica Medica

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Medeiros, Ricardo Miguel Pedroso. "Caracterização preliminar dos níveis de colesterol plasmático em canídeos em função do sexo, raça, idade e condição corporal." Master's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2011. http://hdl.handle.net/10400.5/3580.

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Dissertação de Mestrado Integrado em Medicina Veterinária
Envolvido em múltiplas funções da homeostasia do corpo, o colesterol, depois de absorvido no lúmen intestinal e processado nos enterócitos, entra na corrente sanguínea onde é transportado sob a forma de lipoproteínas as quais se classificam de acordo com a sua densidade, resultante da quantidade e do tipo de apoproteínas e de colesterol que as constituem, em quilomicras, lipoproteínas de muito baixa densidade (VLDL), lipoproteínas de densidade intermédia (IDL), lipoproteínas de baixa densidade (LDL) e lipoproteínas de alta densidade (HDL), sendo esta última a fracção predominante no cão. É sabido que os valores de colesterol e o perfil das lipoproteínas plasmáticas variam em função de um conjunto de factores intrínsecos e extrínsecos ao indivíduo. O presente estudo utilizou uma amostra de 20 indivíduos (n=20) da espécie Canis lupus familiaris, e teve por objectivos: 1) Caracterizar os indivíduos incluídos no estudo quanto ao sexo, raça, idade e condição corporal; 2) Determinar a relação entre os valores plasmáticos de COL e as variáveis consideradas em 1); 3) Determinar a relação entre os valores plasmáticos de HDL-C e as variáveis consideradas em 1); 4) Determinar a relação entre os valores plasmáticos de COL e HDL-C. Os resultados obtidos permitiram concluir que na amostra a média dos valores de COL foi de 223,20±85,54mg/dL, encontrando-se a maioria dos indivíduos (95%) numa situação de normocolesterolémia. Os indivíduos mais velhos, os mais obesos e as fêmeas inteiras, foram os que apresentaram os valores de COL mais elevados. Para o HDL-C, a média foi de 86,02±10,37mg/dL, tendo sido os valores mais elevados registados em fêmeas inteiras, e os mais baixos nos indivíduos obesos. Os testes estatísticos realizados não permitiram contudo excluir a hipótese nula da ausência de diferenças nos valores de COL e de HDL-C, considerando os parâmetros sexo, raça e condição corporal para ambos e ainda, para o HDL-C, o factor idade.
ABSTRACT - Preliminary characterization of plasmatic cholesterol values in dogs based on gender, age, breed and body condition - Playing a role in multiple functions of the body homeostasis, the cholesterol, after being absorbed at intestinal lumen and processed by the enterocyte, reaches bloodstream, where its transport is performed by lipoproteins, classified by their density, which result from its constitution in apoproteins and cholesterol, in chylomicrons, very-low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL), being this last one the predominant fraction in the dog. It is well known that total cholesterol and the profile of plasmatic lipoproteins vary in function of a set of factors, intrinsic and extrinsic to the individuals. The present study used a sample of 20 individuals of Canis lupus familiaris specie, to achieve the following objectives: 1) characterize the individuals included according to their gender, breed, age and body condition; 2) determine a relation between the plasmatic values of COL and the variables considered at 1); 3) determine the existence or not of a relation between the plasmatic values of HDL-C and the variables considered at 1); 4) determine the existence or not of a relation between the plasmatic values of COL and HDL-C. The results showed that the mean of COL values of the sample was 223,20±85,54mg/dL, and the majority of the individuals (95%) were in a situation of normocolesterolemia. The older individuals, the more obese and intact females showed the highest COL values. Concerning the HDL-C, the mean was 86,02±10,37mg/dL, the highest values were seen in intact females, and the lowest values were found in obese individuals. Nevertheless, the statistical tests to whom the sample was submitted did not allowed to exclude the nule hypothesis of the absence of differences in the values of COL and HDL-C considering gender, breed and body condition for both and still, for HDL-C, the age.

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Lindbohm, Nina. "Sialic acid in lipoproteins : with special reference to low density lipoproteins." Helsinki : University of Helsinki, 2000. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/lindbohm/.

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Ooi, Esther M. M. "Regulation of lipoprotein transport in the metabolic syndrome : impact of statin therapy." University of Western Australia. School of Medicine and Pharmacology, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0125.

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[Truncated abstract] The metabolic syndrome is characterized by cardiovascular risk factors including dyslipidemia, insulin resistance, visceral obesity, hypertension and diabetes. The dyslipidemia of the metabolic syndrome includes elevated plasma triglyceride and apolipoprotein (apo) B levels, accumulation of small, dense low-density lipoprotein (LDL) particles and low high-density lipoprotein (HDL) cholesterol concentration. However, the precise mechanisms for this dyslipoproteinemia, specifically low plasma HDL cholesterol, are not well understood. This thesis therefore, focuses on HDL, its structure, function and metabolism. However, lipoprotein metabolism is a complex interconnected system, which includes forward and reverse cholesterol transport pathways. Hence, this thesis also examines and discusses the metabolism of apoB-containing lipoproteins. This thesis tests the general hypothesis that apolipoprotein kinetics are altered in the metabolic syndrome, and that lipid regulating therapies can improve these kinetic abnormalities. The aims were first, to compare and establish the clinical, metabolic and kinetic differences between metabolic syndrome and lean subjects; and second, to determine the regulatory effects of statin therapy, specifically, rosuvastatin on lipoprotein transport in the metabolic syndrome. Five observation statements were derived from the general hypothesis and examined in the studies described below. The findings are presented separately as a series of original publications. Study 1 Twelve men with the metabolic syndrome and ten lean men were studied in a case-control setting. ... These findings explain the HDL raising effects of rosuvastatin in the metabolic syndrome. Collectively, these studies suggest that the dyslipidemia of the metabolic syndrome results from increased production rates of VLDL and LDL particles, reduced fractional catabolic rates of these lipoproteins, together with accelerated catabolism of HDL particles. Treatment with rosuvastatin increases the catabolic rates of all apoB-containing lipoproteins and at a higher dose, decreases LDL apoB production. These effects are consistent with inhibition of cholesterol synthesis leading to an upregulation of LDL receptors. Rosuvastatin decreases the fractional catabolism of HDL particles. The effects of rosuvastatin on HDL kinetics may be related to a reduction in triglyceride concentration and cholesterol ester transfer protein activity. These findings are consistent with the general hypothesis that apolipoprotein kinetics are altered in the metabolic syndrome, and that statin therapy improves these kinetic abnormalities.

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Steiner, Marcelo Luis [UNESP]. "Avaliação comparativa da eficácia da terapia de reposição hormonal de baixa dose isolada ou associada à sinvastatina no perfil lipídico e lipoprotéico em mulheres sintomáticas e dislipidêmicas na pós-menopausa." Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/106365.

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Libbs Farmaceutica
Avaliar comparativamente a eficácia da terapêutica de reposição hormonal (TRH) de baixa dose isolada ou associada à sinvastatina no comportamento de marcadores de risco cardiovasculares e do perfil lipídico e lipoprotéico em mulheres sintomáticas e com dislipidemia na pós-menopausa. Duzentas e quarenta e duas mulheres na pós-menopausa, sintomáticas e com dislipidemia foram randomizadas em três grupos de tratamento: A) estradiol (E2) 1mg/acetato de noretisterona (NETA) 0,5mg [E2/NETA] + sinvastativa 20mg; B) E2/NETA + placebo; e C) sinvastatina 20mg + placebo. A eficácia de cada tratamento foi avaliada pela melhora do perfil lipídico e lipoprotéico e dos sintomas climatéricos ao final de 16 semanas de tratamento. O colesterol total, o LDL-C, o colesterol não-HDL e a Apo B diminuíram de forma significativa (p<0,0001) ao final de 16 semanas no grupo que utilizou E2/NETA + sinvastatina e naquele tratado com sinvastatina + placebo. A relação Apo B/Apo A1 também apresentou redução significativa nestes dois grupos (p<0,0001 e p=0,0026 respectivamente). A Apo A1 diminuiu apenas no grupo que recebeu E2/NETA + sinvastatina (p=0,0055). O grupo E2/NETA + placebo não apresentou alterações significativas no perfil lipídico e lipoprotéico entre as visitas basal e final. Aquele que utilizou E2/NETA + sinvastatina apresentou redução significativa do HDL-C e da Apo A1 quando comparado às usuárias de sinvastatina + placebo (p=0,0233 e p=0,0231 respectivamente). No alívio dos sintomas climatéricos, os grupos que utilizaram E2/NETA foram superiores a sinvastatina + placebo. Em mulheres na pós-menopausa com dislipidemia, a associação de E2/NETA em baixa dose com sinvastatina aliviou os sintomas climatéricos de forma semelhante à observada com a E2/NETA isolada e melhorou o perfil lipídico e lipoprotéico de modo semelhante ao uso isolado da sinvastatina. O uso de E2/NETA sem...
To evaluate low-dose hormone therapy (HT) + simvastatin for vasomotor symptoms and cardiovascular risk markers. Symptomatic postmenopausal women (n=242) with dyslipidemia were randomized to one of three treatment groups: A) 1mg estradiol/0.5mg norethisterone acetate (E2/NETA) + 20mg simvastatin; B) E2/NETA + placebo; or C) 20mg simvastatin + placebo. Lipid and lipoprotein profiles and menopausal symptoms were evaluated after 16 weeks. Total cholesterol, LDL cholesterol, non-HDL cholesterol and Apo-B decreased (p<0.0001) in groups A and C, as did Apo-B/Apo-A1 (p<0.0001 and p=0.0026, respectively). Apo-A1 decreased only in group A (p=0.0055). HDL cholesterol and Apo-A1 were lower in A than C (p=0.0233 and p=0.0231, respectively). Relief of menopausal symptoms was better in A and B compared to C. HT + simvastatin were effective for the treatment of symptomatic postmenopausal women and improved the lipid profile similar to simvastatin alone. It also delivered an improvement in the simultaneous treatment of menopausal symptoms and dyslipidemia

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Hacquebard, Mirjam Rebecca. "Alpha-tocopherol acquisition by plasma lipoproteins and changes in lipoprotein profile after cardiac surgery." Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/216586.

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Alpha-tocopherol, the most abundant form of vitamin E in man, is transported in the circulation by plasma lipoproteins. It plays important roles, not only in preventing lipid peroxidation, but also in modulating several cell functions such as cell signaling and gene expression. While chylomicrons transport dietary alpha-tocopherol after intestinal absorption, LDL and HDL are the major carriers of alpha-tocopherol in fasting plasma and largely contribute to its delivery to cells and tissues. Exchanges of alpha-tocopherol occur between plasma lipoproteins. In addition, alpha-tocopherol transfers have also been observed, in both directions, between plasma lipoproteins and artificial chylomicrons such as intravenous lipid emulsion particles used in parenteral nutrition. In acute conditions, intravenous supply of vitamin E via lipid emulsions, which bypasses the intestinal tract, may offer some advantages over oral administration to rapidly increase alpha-tocopherol plasma concentration. However, many questions remain unanswered regarding kinetics and factors facilitating vitamin E exchanges between lipid emulsions and plasma lipoproteins. The first part of this work aimed at characterizing alpha-tocopherol transfers between alpha-tocopherol rich emulsion particles and plasma lipoproteins as well as the potential for plasma proteins to modulate such transfers. An in vitro model of incubation was used in which emulsion triglyceride concentration was relatively low and lipoprotein levels comparable to those commonly found in the circulation. Results indicate a high capacity for LDL and HDL to acquire extra-amounts of alpha-tocopherol by rapid mass transfers from alpha-tocopherol-rich emulsion particles. Data further shows that, at a fixed alpha-tocopherol concentration provided by emulsion particles, the limiting factor for alpha-tocopherol enrichment is not the capacity of plasma lipoproteins to accommodate extra-amounts of alpha-tocopherol but the facilitating effect of plasma proteins on alpha-tocopherol transfer, the duration of the incubation and possibly the competition between different acceptor particles. Two lipid transfer proteins, PLTP and CETP, appear to largely mediate facilitation of alpha-tocopherol transfer; however, other plasma proteins may be involved. Data further shows that alpha-tocopherol enriched LDL and HDL can readily transfer newly acquired alpha-tocopherol to cells, without any regulation by plasma proteins.

Short-term prophylactic vitamin E supplementation has been suggested to be beneficial in some patients in acute conditions who present reduced plasma vitamin E concentrations in association with important changes in plasma lipids and severe oxidative stress. However, it was not clear whether low plasma vitamin E concentration in critically ill patients is related to changes in the composition of plasma lipoproteins or to a decrease in the number of alpha-tocopherol carriers. In the second part of this work, two clinical studies were conducted to analyze changes of lipoprotein concentration and composition in relation to inflammatory reaction and oxidative stress in selected subgroups of critically ill patients, namely patients undergoing cardiac surgery with different procedures. Important changes in LDL and HDL lipid content were observed, some of which contrast with previous observations made in critically ill septic patients. The reduced plasma level of alpha-tocopherol measured after cardiac surgery is entirely due to a reduced number of circulating LDL and HDL particles. Data suggests that such reduced number in alpha-tocopherol carriers post-surgery may impede the delivery of alpha-tocopherol to cells in conditions of increased requirements due to oxidative stress. Avoidance of extracorporeal circulation during cardiac surgery does not reduce inflammation-related changes in plasma lipids but largely prevents oxidative stress. This data on changes occurring in plasma lipoproteins may help to better define strategies against pro-inflammatory changes or oxidative stress. If further studies would confirm a clinical benefit with evidence-based rationale, alpha-tocopherol enriched lipid emulsions may be used to guarantee a sufficient alpha-tocopherol supply in acute conditions associated with fewer alpha-tocopherol transporters and increased requirements due to high risk of oxidative tissue injury.

Doctorat en Sciences biomédicales et pharmaceutiques
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Kinchoku, Harumi. "Efeitos do aconselhamento nutricional em pacientes dislipidemicos segundo sexo, idade e tempo de tratamento." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309024.

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Orientador: Eliana Cotta de Faria
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Os principais determinantes da dieta que elevam as concentraçoes de LDL-C sao as gorduras saturadas, gorduras trans e, em menor grau, o colesterol da dieta. O aumento relativo na proporçao de carboidratos resulta em dislipidemia caracterizada pelo aumento das concentrações plasmáticas de TG e VLDL-C, baixas concentrações de HDL-C, razão C:HDL aumentada e, algumas vezes, a presença de partículas de LDL-C pequenas e densas.O propósito deste estudo foi avaliar o impacto do aconselhamento nutricional exclusivo em portadores de dislipidemias,verificando a resposta entre sexos e entre faixas etárias (<60 anos e = 60 anos) e a influência do tempo no tratamento (3,6 e 12 meses). Participaram do estudo 129 sujeitos, 56 homens e 73 mulheres com idade entre 20 a 73 anos sem uso de medicaçao hipolipemiante por no mínimo 30 dias antes e durante o tratamento, e com pelo menos três meses de seguimento nutricional. Para hipercolesterolemia foi orientada a restrição de gorduras saturadas (<7% do VET) e colesterol (<200 mg/dL) e, para hipertrigliceridemia a restriçao de carboidratos simples, bebidas alcoólicas e, restrição de gorduras totais (<20% do VET) para TG>300 mg/dL. Na presença de sobrepeso ou obesidade foi orientada dieta hipocalórica com redução gradativa das calorias. As concentrações de colesterol (C), LDL-C, e triglicérides (TG) foram significativamente reduzidas na população estudada em 14%, 5%, 30% respectivamente. No primeiro trabalho, em que foi avaliada a influência do tempo de aconselhamento nutricional comparado ao período basal, as respostas significativas às orientações dietéticas com três meses foram: para C (-16%), LDL-C (-0,1%) e não HDL-C (-19%); com seis meses para C (-13%), TG (-30%), LDL-C (-9%), nao HDL-C (-17%), Castelli I (-14%) e Castelli II (-4%) e, com 12 meses para C (-14%), TG (-27%) e Castelli I (-13%). As concentrações plasmáticas de HDL-C e o peso corporal não se modificaram. Entre os sexos (trabalho 2) foi observado uma redução de 16% para C e 36% para TG em homens, e de 12% para C, 12% para LDL-C, e 26% para TG nas mulheres e, entre faixa etária de 15% para C, 2% para LDL-C e 33% para TG nos adultos e 14% para C nos idosos. O aumento na concentração de HDL-C foi significativa em homens em relação às mulheres (+5% e -4 %) com hiperlipidemia mista.Todos os participantes responderam ao aconselhamento nutricional reduzindo as concentrações de C, TG, LDL-C e a nao HDL-C. O tempo de orientação dietética não modificou as respostas em lípides e lipoproteínas plasmáticos; sendo o tempo de três meses suficiente para observar os efeitos benéficos da dieta. Um maior número de parâmetros foi reduzido com seis meses indicando que a partir de sexto mês houve um efeito mais abrangente da dieta. Homens e adultos foram mais responsivos à orientação nutricional. As respostas foram maiores que os coeficientes de variação biológico para cada parâmetro avaliado exceto para LDL-C.Recomenda-se a aplicação desta experiência terapêutica positiva em outros Serviços de Saúde por se tratar de uma terapia de baixo custo podendo também contribuir na prevenção e controle de doença cardiovascular
Abstract: The strongest dietary determinants of elevated LDL cholesterol concentrations are dietary saturated fatty acid and trans fatty acid intakes to a lesser extent, dietary cholesterol and excess body weight The aim of the present study was to evaluate the responses plasma lipid to nutritional counseling on dyslipidemic outpatients and analyze their responses by gender and age and analyzing the influence of time (3, 6 and 12 months) of treatment. One-hundred and twenty nine dyslipidemic subjects i.e. 56 males and 73 females aged 20 - 73 years comprised this study. No medication was used 30 days before and during following the diet as part of the inclusion criteria. Patients with hypercholesterolemia were oriented to follow the NCEP step 2 diet, and those with hypertriglyceridemia were oriented to restrict simple carbohydrates and alcoholic beverage and, in presence of TG >300 mg/dl, to use low fat diet (=20%). After nutritional counseling plasma cholesterol (C) concentrations, LDL-C, and triglycerides (TG) were significantly reduced in the population sample by (14%, 5%, 30%), respectively. The response were significant after 3 months for C (-16%), LDL-C (-0,1%) and NHDL-C (-19%), after 6 months for C (-13%), TG (-30%), LDL-C (-9%), NHDL-C (-17%), Castelli I (-14%) and Castelli II (-4%) and, after 12 months for C (-14%), TG (-27%) and Castelli I (-13%). No change was detected in plasma HDL-cholesterol and body weight, after nutritional counseling. Between sexes plasma concentrations reduced for C and TG by 16%, and 36% in men, and by 12% and 26% and 12% for LDL-C in women, and between age by 15% to C, 2% to LDL-C and 33% to TG in middle age and, 14% for C in elderly people. HDL cholesterol concentration was significantly higher in men than in women with mixed hyperlipidemia (+5% and -4 %). All participants responded to nutritional counseling reducing C, TG, LDL-C, NHDL-C, LDL-C. The nutritional counseling time did not modify the responses of plasma lipids and lipoproteins. After 3 months, beneficial effects of the diet were observed, and the higher number of parameters were reduced after 6 month showing a broader actions of diet. Men and adults patients presented better responses to nutritional counseling. The responses to nutritional counseling were higher than coefficient biology variation for each parameter evaluated except to LDL-C. We recommend this positive experience is recommended to other Health Service because is low cost treatment and also contribute in prevention and control of risk factors for cardiovascular disease
Mestrado
Ciencias Basicas
Mestre em Clinica Medica

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Carulla, i. Sanmartí Pere. "Isoformes de pI de la lipoproteïna lipasa: Origen, distribució i funció." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/462027.

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Un dels principals aspectes que hem descrit ha estat la presència i la distribució de les isoformes de pI de l’LPL. Inicialment hem treballat amb teixits de rata adulta: cor, TAB, TAM i múscul. Els resultats han demostrat que tots els teixits de rata dels quals s’ha pogut purificar parcialment l’LPL presenten isoformes de pI de l’LPL. També hem treballat en una de les poques situacions en què el fetge expressa LPL: en cries de rata. Lamentablement, l’LPL ha resultat ser una proteïna difícilment purificable. A les cries de rata, però, hem pogut descriure clarament la presència d’isoformes de l’LPL al cor i al TAM. A partir de tota la informació obtinguda de la descripció d’isoformes en teixits de rata, hem dissenyat un mètode per modelitzar el patró d’isoformes de cada teixit, determinat pel nombre d’isoformes, i el pI i l’abundància relativa de cada isoforma. Aquesta modelització ens ha permès comparar els patrons obtinguts en cada purificació i determinar la similitud dels patrons d’isoformes entre diferents teixits i diferents espècies. La presència de les isoformes en sí ja és un fet molt important pel coneixement de l’LPL. Però el fet d’haver descrit diferències entre els patrons d’isoformes entre els teixits de rata, va posar de manifest la rellevància de la funció diferencial de l’LPL en cada teixit. A partir d’aquesta idea hem estudiat la funció de les isoformes de pI de l’LPL. Com està àmpliament descrit, l’expressió i l’activitat de l’LPL és depenent de cada teixit i de la situació fisiològica en què es trobi l’animal. Hem descrit els patrons de l’LPL de diferents teixits de rata (cor, TAB i TAM) en situacions fisiològiques en les quals és sabut que l’activitat LPL varia notablement (fred, dejuni i realimentació) respecte a la situació control. Mitjançant el pI i la abundància relativa de les isoformes de tots els teixits de rata, hem dissenyat un sistema de classificació de les isoformes en poblacions segons clústers. Aquesta caracterització de les isoformes en clústers permet descriure les variacions que hi ha entre diferents situacions o teixits des d’un enfocament totalment diferent al tractat fins aleshores. Hem pogut detectar importants variacions en les poblacions de les isoformes de pI segons la situació fisiològica. Paral·lelament, hem estudiat l’afinitat de les isoformes de pI de l’LPL tant per l’ancoratge (heparina) com pel substrat. Entre les diferents isoformes no hem descrit diferències d’afinitat per heparina i totes presenten activitat LPL. Tot i això, no podem descartar petites diferències d’afinitat pel substrat. Del TAB visceral de macaco, n’hem descrit la presència d’isoformes de pI de l’LPL i el seu patró de distribució. Totes les isoformes de pI del TAB d’aquesta espècie també presenten afinitat pel substrat i, per tant, activitat LPL. A més, també són degudes, parcialment, a la glicosilació de la proteïna. Ens hem plantejat determinar quines són les característiques que determinen l’origen les isoformes de pI de l’LPL. A partir de la purificació del TAB de macaco, hem determinat de novo d’un 74% de la seqüència de l’LPL. En aquesta cobertura, hem pogut confirmar la presència de l’asparagina 44 i les tirosines 95 i 165. Aquests aminoàcids estan descrits en altres espècies com a objectius de modificacions posttraduccionals. A continuació, hem treballat per separar les isoformes de pI, les unes de les altres, mitjançant l’isoelectroenfocament en líquid (off-gel electrophoresis). L’objectiu d’aquest treball ha estat poder treballar amb les isoformes per separat i determinar quina combinació de modificacions posttraduccionals és la responsable de cada isoforma. Novament, probablement a causa de les característiques de l’LPL, ens ha resultat impossible obtenir la purificació de cada isoforma
We have described has been the presence and distribution of the pI isoforms of LPL. We have worked with adult rat tissues: heart, WAT, BAT and muscle. The results have shown that all tissues have LPL isoforms. In 15-days old rats, the LPL expressed in the liver LPL has turned out to be a protein that is hard to purify. However, we have been able to clearly describe the presence of isoforms of LPL in heart and BAT. We have designed a method for modelling the isoform pattern of each tissue, determined by the number of isoforms, and the pI and the relative abundance of each isoform. This modelling has allowed us to compare the patterns and to determine the similarity of isoform patterns. We have studied the function of the pI isoforms of LPL. The expression and activity of the LPL is dependent on each tissue and the physiological situation in which the animal is found. We have described the LPL patterns of different rat tissues (heart, TAB and TAM) in physiological situations in which LPL activity is known to vary markedly (cold, fasting and refeeding) compared to the control animals. By means of the pI and the relative abundance of the isoforms of all the rat tissues, we have designed a system of classification of the isoforms in populations according to clusters. This characterization of isoforms in clusters allows describing the variations that exist between different situations or tissues from a totally different approach to the one treated until now. At the same time, we have studied the affinity of the pI isoforms of LPL for the anchor (heparin) and the substrate. Among the different isoforms we have not described differences in affinity and all isoforms are active. We have described the presence of pI isoforms of LPL and its distribution pattern of the WAT of Macaca fascicularis. In addition, they are also partially due to glycosylation of the protein. We have described 74% of the sequence of the LPL. In this coverage, we have been able to confirm the presence of asparagine 44 and tyrosine 95 and 165. These amino acids are described in other species as targets for posttranslational modifications.

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Downs, Leonie Grace. "Canine lipoproteins and apolipoproteins." Thesis, University of Bristol, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296663.

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16

Chen, Shwu-Pyng T. "Lipoproteins in human milk /." The Ohio State University, 1986. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487264603219615.

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17

Barrett, P. Hugh R. "The kinetic analysis and computer modelling of lipoprotein metabolism in man." Title page, table of contents and abstract only, 1989. http://web4.library.adelaide.edu.au/theses/09PH/09phb274.pdf.

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18

Panzoldo, Natália Baratella 1987. "Características fenotípicas e funcionais da lipoproteína de alta densidade (HDL) na hipoalfalipoproteinemia e na aterosclerose subclínica = Phenotypical and functional characteristics of high-density lipoprotein (HDL) on hypoalphalipoproteinemia or subclinical atherosclerosis." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312487.

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Orientadores: Andrei Carvalho Sposito, Eliana Cotta de Faria
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-25T13:48:30Z (GMT). No. of bitstreams: 1 Panzoldo_NataliaBaratella_D.pdf: 2220803 bytes, checksum: b1c1a7df4771466e6a32411bceb02387 (MD5) Previous issue date: 2014
Resumo: Doenças cardiovasculares constituem a principal causa de mortalidade no Brasil e no mundo. Baixas concentrações de HDL - colesterol são consideradas um fator de risco cardiovascular independente. Esta relação inversa tem sido atribuída às diferentes propriedades protetoras da HDL, dentre as quais podemos destacar seu papel no transporte reverso de colesterol, por meio do efluxo de colesterol, sua habilidade de inibir a agregação plaquetária, e suas atividades antioxidantes e anti-inflamatórias. No entanto, estudos recentes indicam que baixas concentrações de HDL - colesterol constituem um preditor significante de doença aterosclerótica somente em indivíduos assintomáticos e que a capacidade de efluxo de colesterol é um melhor preditor de carga aterosclerótica do que HDL - colesterol. Em conjunto, estes achados sugerem que a função da HDL poderia ser um fator chave na relação entre concentrações de HDL - colesterol e o desenvolvimento de doença aterosclerótica. Se o for, alterações das funções da HDL podem discernir melhor, entre os indivíduos com hipoalfalipoproteinemia, aqueles com maior propensão a desenvolver doença aterosclerótica. Assim, investigamos, em indivíduos sem doença cardiovascular previamente manifesta, se funções da HDL estão associadas a concentrações de HDL - colesterol e carga aterosclerótica. Participantes foram classificados em HDL - colesterol baixo (LH; HDL-C? 32 mg/dL; n=33), intermediário (IH; HDL-C= 40-67 mg/dL; n=33), ou alto (HH; HDL-C?78mg/dL; n=35). Nós avaliamos composição química da HDL, tamanho da partícula, capacidade de efluxo de colesterol, atividade antioxidante, susceptibilidade à oxidação, atividade anti-inflamatória, e habilidade de inibir agregação plaquetária. O grupo LH foi associado à espessura intimo-medial de carótidas (IMT) aumentada (p?0,001), maior conteúdo de triglicérides (4±2% vs. 4±2% em IH e 3±1% em HH, p?0,001), menor conteúdo de fosfolípides (12±4% vs. 14±5% em IH e 13±3% em HH, p=0,035), menor tamanho de partículas (7,33±0,33nm vs. 7,72±0,45nm em IH e 8,49±0,42nm em HH, p?0,001) e menor capacidade de efluxo de colesterol celular (9±3 % vs. 12±3 % em IH e 11±4 % em HH, p?0,001). Indivíduos HH apresentaram menor atividade antioxidante (37(53)% vs. 48(35)% em IH e 55(41)% em LH, p=0,003), maior suscetibilidade à oxidação (57±22% vs. 45±20% em IH e 46±25% em LH, p=0,017) e maior habilidade de inibir agregação plaquetária (45±25% vs. 31±18% em IH e 37±24 % em LH, p=0,0026). Indivíduos com IMT acima de 1 mm apresentaram partículas com menor tamanho (7,55±0,49 nm vs. 7,89±0,64 nm, p?0,001), atividade antioxidante (37(23)% vs. 49(42)%, p=0,018) e capacidade de efluxo de colesterol (31±14% vs. 40±14%, p=0,02). Nenhuma diferença foi encontrada para as outras características ou propriedades funcionais da HDL. Nós concluímos que, em um contexto de prevenção primária, o menor tamanho da partícula, o conteúdo reduzido de fosfolípides, e capacidade de efluxo de colesterol diminuída são relacionados com ambos LH e magnitude da doença aterosclerótica subclínica. Nestes indivíduos, estas características podem explicar a associação entre HDL - colesterol e o desenvolvimento da doença aterosclerótica.
Abstract: Cardiovascular diseases are the main cause of death in Brazil and worldwide. Low HDL-C levels are considered an independent cardiovascular risk factor. This inverse relationship has been attributed to different protective properties described for HDL, such as its role in the reverse cholesterol transport, through cholesterol efflux, its ability to inhibit platelet aggregation, and its antioxidant and anti-inflammatory effects. However, recent studies indicate that low HDL-cholesterol is a significant predictor of atherosclerotic disease in healthy individuals and that cholesterol efflux capacity is a better predictor of carotid atherosclerotic burden as compared to HDL-cholesterol. Altogether these findings have suggested that HDL function would be the key factor for the link between HDL-cholesterol concentration and the subclinical disease in a primary prevention setting. If so, changes in HDL function could help to discriminate, among individuals with hypoalphalipoproteinemia, those who are prone to develop atherosclerotic disease. Hence, in a primary prevention setting, we investigated whether HDL dysfunction is associated with HDL-cholesterol concentration and atherosclerotic burden. Participants were classified as low (LH; HDL-C? 32 mg/dL; n=33), intermediate (IH; HDL-C= 40-67 mg/dL; n=33), or high HDL-cholesterol (HH; HDL-C?78mg/dL; n=35). We measured HDL chemical composition, particle size, cholesterol efflux capacity, antioxidant activity, susceptibility to oxidation, anti-inflammatory activity, and ability to inhibit platelet aggregation. LH was associated to enhanced carotid intima-media thickness (IMT;p?0.001), high HDL triglyceride (4±2% vs. 4±2% in IH and 3±1% in HH, p?0.001), low HDL-phospholipids (12±4% vs. 14±5% in IH and 13±3% in HH, p=0.035), decreased particle size (7.33±0.33nm vs. 7.72±0.45nm in IH and 8.49±0.42nm in HH, p?0.001) and reduced cholesterol efflux capacity (9±3 % vs. 12±3 % in IH and 11±4 % in HH, p?0.001). The HH group presented reduced antioxidant activity (37(53)% vs. 48(35)% in IH and 55(41)% in LH, p=0.003), and increased susceptibility to oxidation (57±22% vs. 45±20% in IH and 46±25% in LH, p=0.017) and ability to inhibit platelet aggregation (45±25% vs. 31±18% in IH and 37±24 % in LH, p=0.0026). Carotid IMT>1mm was associated with reduced HDL size (7.55±0.49 nm vs. 7.89±0.64 nm, p?0.001), antioxidant activity (37(23)% vs. 49(42)%, p=0.018), and cholesterol efflux capacity (31±14% vs. 40±14%, p=0.02). No differences were found for the other HDL characteristics or functional properties. We conclude that in a primary prevention setting, small particle size, reduced HDL-phospholipids content, and diminished cholesterol efflux capacity are related to both LH and carotid IMT. In these individuals, these characteristics may underlie the association between HDL-cholesterol and atherosclerotic burden
Doutorado
Ciencias Biomedicas
Doutora em Ciências Médicas

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19

Owen, Alice. "The effects of estrogens and phytoestrogens on the metabolism and oxidation of plasma lipoproteins /." Title page, contents and abstract only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09pho968.pdf.

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20

Lynn, Edward G. "The role of lipoproteins in the development of glomerulosclerosis : y Edward G. Lynn." Thesis, Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B22142484.

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21

Daugherty, Alan. "Lipoproteins, inflammation, and vascular disease." Thesis, University of Bath, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425851.

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The major focus of the studies described in this thesis is the interaction of lipoproteins and inflammation in vascular diseases. Early studies describe the role of postprandial lipoproteins in the development of lipid-laden macro phages that are a hallmark of atherosclerotic lesions. These studies paved the way for subsequent studies on the role of lipoprotein modification in atherosclerosis. These included the discovery that LDL present in atherosclerotic lesions had properties that were consistent with oxidative modification. To determine whether this modification was a cause or consequence of the disease, studies were performed using antioxidants. These studies defined the effects of antioxidants on early and mature atherosclerotic lesions, as well as on iatrogenic vascular lesions. My laboratory also studied two potential enzymes that have the potential to generate oxidized lipoprotein; myeloperoxidase and 15-lipoxygenase. The effects of pharmacological inhibition and regulation on the latter enzyme were defined. Studies have also addressed the regulation and function of a major receptor for oxidized LDL, class A scavenger receptor. These include regulation, structure-function, and the effects of cell selective overexpression. These lipoprotein modifications have a well characterized role on the infiltration of macro phages and their subsequent engorgement with lipid. Aberrant lipoprotein metabolism may be a factor underlying the recruitment of T Iymphocytes into lesions. Generally, T Iymphocytes have an under appreciated role in the atherogenic process. Studies using mice deficient in Iymphocyte subclasses and specific cytokines are addressing the issue of this cell type in lesion formation. Finally, we have recently discovered a pronounced inflammatory role of angiotensin II that is associated with the development of atherosclerosis and abdominal aortic aneurysms

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22

Gray, E. "Lipoproteins, blood coagulation and thrombosis." Thesis, Open University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372834.

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The main aim of this study was to investigate the involvement of plasma lipoproteins in the blood coagulation system and the implications of this relationship in the pathogenesis of thrombosis. This study has shown that lipid peroxide-induced thrombin generation is caused by a two-fold mechanism: direct interaction of lipid peroxides with lipoprotein phospholipids and inhibition of anti-thrombin III via its heparin-binding site. Experiments using purified lipoproteins have shown that triglyceride-rich lipoproteins, i.e. chylomicra and very low density lipoproteins, are sources of procoagulant activity, whereas low density and high density lipoproteins have little effect. Further work with phospholipids extracted from chylomicra has demonstrated that lipid peroxides interact with the phospholipid component of the lipoprotein molecule and, possibly through an increase in overall negative charge, provide a suitable surface for the binding of clotting factors. Subcutaneous injection of potent lipase releasers, which are weak in vitro anticoagulants, reduce the ex vivo thrombin-generating activity of post-infusion plasma. This reduction in procoagulant activity is caused by the phospholipase action of the hepatic tri-glyceride lipase (HTGL) released. Human HTGL also enhances plasma anti-Xa activity, due to direct inhibition of Xa clotting activity, but the amidolytic activity of Xa is unaffected, thus implying that the serine site of Xa is not preferentially targeted. The phospholipid binding site of Xa appears to be involved, but this anti-Xa effect is not due to the phospholipase action of HTGL. The antithrombotic effects of heparin and heparin analogues may thus be partly due to the release of HTGL, which can reduce pro-coagulant activity via inhibition of lipid peroxide-induced thrombin generation and enhancement of plasma anti-Xa activity.

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23

Fazolo, Demétria Luci. "Estudo da interação de prováveis lipoproteínas de membrana externa de Leptospira com proteínas do hospedeiro." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-06122014-085815/.

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A leptospirose é uma zoonose mundial causada por espiroquetas patogênicas do gênero Leptospira, que colonizam os túbulos renais de animais domésticos e silvestres e são liberadas ao ambiente externo pela urina. Neste estudo avaliou-se a interação de seis prováveis lipoproteínas de membrana externa de leptospira com as proteínas do hospedeiro: colágeno I, colágeno IV, elastina, fibrinogênio, fibronectina celular e plasmática, laminina e plasminogênio. Os experimentos de adesão demonstraram que as proteínas recombinantes Lp21, Lp22 e Lsa30 apresentaram interação com os componentes do hospedeiro de maneira dose-dependente. Estas aderiram à fibronectina plasmática e laminina, além destes, a Lp21 e a Lp22 interagiram com plasminogênio, a Lp22 e a Lsa30 interagiram com colágeno IV. A Lp22 aderiu à elastina e ao fibrinogênio. No estudo de conservação gênica, os genes que codificam estas proteínas foram observados somente nas Leptospiras patogênicas. Portanto estas proteínas devem contribuir na adesão aos tecidos do hospedeiro na patogênese da Leptospira.
Leptospirosis is a worldwide zoonosis caused by pathogenic spirochetes of the genus Leptospira that colonize the renal tubules of wild and domestic animals and are excreted in the environment by their urine. The aim of this work was to study the interaction of six leptospiral probable outer-membrane lipoproteins with host proteins: collagen I, collagen IV, elastin, fibrinogen, cellular fibronectin, plasma fibronectin, laminin, and plasminogen. The binding experiments demonstrated that the recombinant proteins showed interaction with host components in a dose-dependent manner were Lp21, Lsa30 and Lp22. These proteins adhered to plasma fibronectin and laminin, in addition to these components, Lp21 and Lp22 interacted with plasminogen, Lp22 and Lsa30 interacted with collagen IV. The Lp22 adhered to elastin and fibrinogen. The genes encoding the probable lipoproteins were found only in pathogenic Leptospira. These results demonstrated that these proteins may contribute in the adhesion to host tissues, in the pathogenesis of Leptospira.

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24

Sobot, Dunja. "Nanoparticules squalenisées et lipoprotéines plasmatiques : caractérisation des interactions moléculaires et évaluation de leur implication dans la réponse thérapeutique." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS419/document.

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Après administration intraveineuse, un nanovecteur va interagir avec de nombreuses molécules endogènes, notamment celles présentes dans la circulation sanguine. En fonction de la composition chimique du nanovecteur, ces molécules vont conférer à celui-ci une signature spécifique qui va orienter sa biodistribution et sa reconnaissance par certaines cellules de l’organisme. Plusieurs études sur l'identification des protéines adsorbées à la surface des nanovecteurs ont été menées alors que moins d'attention a été consacrée à l'interaction avec les lipoprotéines (LPs). Or, un nombre élevé de récepteurs aux LPs a été observé dans les cellules à croissance rapide et des études ont démontré que certaines cellules cancéreuses surexpriment ces récepteurs. De ce fait, l’utilisation des LPs comme vecteurs de médicaments anticancéreux a été proposée afin de favoriser le ciblage des cellules tumorales. Ce projet de thèse repose sur l’utilisation d’un bioconjugué (SQGem) issu du couplage chimique de la gemcitabine (Gem), une molécule anticancéreuse, au squalène (SQ) (un lipide naturel et précurseur de la biosynthèse du cholestérol), dont l’auto-organisation sous forme de nanoparticules à préalablement été décrite au laboratoire. Nous avons pu mettre en évidence la capture et le transport spontané de la SQGem par les LPs plasmatiques. Les résultats in vitro et in vivo que nous avons obtenus démontrent parfaitement que l’association préférentielle de la SQGem aux LPs corrèle fortement avec la quantité de cholestérol présente dans ces derniers. De plus, les simulations in silico effectuées ont révélé l’incorporation de SQGem dans le noyau hydrophobe des LPs. Par la suite, cette interaction spontanée a été mise à contribution pour effectuer le ciblage indirect des cellules cancéreuses ayant une expression élevée de récepteurs aux LPs, ce qui a été confirmé in vitro sur cellules ainsi qu’in vivo sur un modèle de tumeur expérimentale chez la souris. L’ensemble de ces résultats suggère l’originalité de notre approche, basée sur le ciblage des tumeurs de manière indirecte via les LPs qui constituent ainsi des « vecteurs » endogènes de SQGem. La « squalénisation » évite ainsi la préparation fastidieuse de vecteurs à base de LPs reconstitués et représente, par l’utilisation des LPs endogènes, une stratégie innovante et potentiellement révolutionnaire dans le traitement expérimental du cancer
The in vivo fate of intravenously injected nanoparticles is strongly affected by their interactions with the blood components. Several studies have focused on the identification of proteins adsorbed at the surface of nanoparticles whereas less attention has been devoted to the interaction with lipoproteins (LPs). Interestingly, LPs have been previously described as excellent carriers for delivery of anticancer drugs due to their particularly high receptor-mediated uptake on several cancer cell lines. In this PhD project, we focused on a bioconjugate obtained by covalent linkage of the anticancer drug gemcitabine (Gem) to squalene (SQ) (a natural lipid and precursor of the cholesterol’s biosynthesis) whose ability to spontaneously self-assemble in the form of nanoparticles has been previously described in our laboratory. We have demonstrated that this conjugation enables the spontaneous capture and transport of the SQGem by circulating lipoproteins. In vitro and in vivo experiments revealed a preeminent affinity of SQGem towards cholesterol-rich LP particles and in silico simulations further displayed their incorporation into the hydrophobic core of LPs. Such spontaneous interaction allowed for indirect targeting of cancer cells with high expression of LP receptors, which was confirmed both in vitro and in vivo in an experimental tumor model in mice. To the best of our knowledge, the use of squalene to induce drug insertion into LPs for indirect cancer cell targeting is a novel concept in drug delivery. It represents a flexible, highly versatile platform that would enable efficient drug delivery by simply exploiting endogenous lipoproteins without the need for complex nanoparticles surface functionalization or artificial lipoproteins production

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25

Hernáez, Camba Álvaro. "Effects of the mediterranean diet and virgin olive oil on the function of high-density lipoproteins and the atherogenicity of low-density lipoproteins in humans." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/399414.

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Cardiovascular diseases are the main cause of death worldwide and a relevant source of economic cost and physical disability. The Mediterranean Diet, associated with a high intake of virgin olive oil, has been shown to be protective against the development of cardiovascular diseases. Adherence to the Mediterranean Diet and the consumption of virgin olive oil induce this protection by improving several cardiovascular risk factors, such as the lipid profile. These two dietary interventions are known to increase cholesterol levels in high-density lipoproteins (HDLs) and decrease cholesterol concentrations in low-density lipoproteins (LDLs). However, it is becoming increasingly more accepted that the information provided by HDL and LDL cholesterol levels is quite limited. On the one hand, the biological functions of HDLs may reflect the anti-atherogenic role of the lipoprotein better than HDL cholesterol levels. On the other hand, several LDL characteristics beyond LDL cholesterol levels, such as the pro- atherogenic LDL traits (LDL size, oxidation, composition, etc.), may be more informative with respect to the unexplained cardiovascular risk of an individual. Nevertheless, despite their growing relevance, very few randomized controlled trials have examined the effects of healthy lifestyle modifications on these properties. The aim of the present thesis project was to assess whether adherence to the Mediterranean Diet or the consumption of virgin olive oil was able to increase HDL functionality and decrease LDL pro-atherogenic traits in humans. Samples in the present project were obtained from two randomized controlled trials: the EUROLIVE Study (Effects of Olive Oil Consumption on Oxidative Damage in European Populations) and the PREDIMED Study (Effects of Mediterranean Diet on the Primary Prevention of Cardiovascular Disease). In both cases, we isolated HDLs and LDLs in different sub-samples from volunteers in order to perform a complete battery of determinations related to HDL function and LDL atherogenicity. The consumption of virgin olive oil increased the main HDL function: its cholesterol efflux capacity. An increase in the content of olive oil phenolic compounds in HDL, as well as the enhancement of HDL composition and size, may explain the functional improvement. Regarding the Mediterranean Diet, increasing adherence to this dietary pattern improves the four main HDL functions: cholesterol efflux capacity, HDL role in other steps of reverse cholesterol transport, HDL antioxidant activities, and HDL vasodilatory capacity. An improvement in HDL oxidation, size, and composition may also justify HDL enhanced function. In addition, the consumption of virgin olive oil decreased LDL levels and LDL atherogenicity (increasing LDL size and resistance against oxidation). Adherence to the Mediterranean Diet also improved LDL pro-atherogenic traits, by increasing LDL size and resistance against oxidation, decreasing LDL oxidation in vivo, improving LDL composition, and decreasing LDL cytotoxicity in macrophages. In conclusion, the present PhD thesis project shows that the consumption of virgin olive oil and adherence to the Mediterranean Diet improved HDL function and LDL pro- atherogenic traits in humans in two randomized controlled trials. Our findings provide two novel mechanisms to explain part of the benefits of these healthy diet interventions, and support previous evidence concerning the cardioprotective role of virgin olive oil and the Mediterranean Diet in humans.
Les malalties cardiovasculars són la principal causa de mort en el món i una rellevant font de despesa social i discapacitat física. La Dieta Mediterrània, associada a un alt consum d’oli d’oliva verge, ha demostrat ser protectora davant el desenvolupament de malalties cardiovasculars. L’adherència a una Dieta Mediterrània o la ingesta d’oli d’oliva verge indueixen aquesta protecció millorant nombrosos factors de risc cardiovascular, com el perfil lipídic. Ambdues intervencions són capaces d’incrementar els nivells de colesterol en lipoproteïnes d’alta densitat (HDL, en les seves sigles en anglès) i de disminuir les concentracions de colesterol en lipoproteïnes de baixa densitat (LDL, en les seves sigles en anglès). Però, cada vegada s’accepta més que la informació proporcionada pels nivells de colesterol HDL i LDL és limitada. Per un costat, l’anàlisi de les funcions biològiques de les HDLs han reflectit el paper anti- aterogènic de la lipoproteïna millor que els nivells de colesterol HDL. Per un altre, certes característiques de les LDLs més enllà dels seus nivells de colesterol, com els trets pro-aterogènics de les LDLs (grandària, oxidació, composició, etc.), podrien ser més informatives del risc cardiovascular residual dels individus. No obstant això, i malgrat la seva creixent rellevància, molt pocs assajos clínics aleatoritzats i controlats han estudiat els efectes protectors d’intervencions dietètiques saludables sobre aquestes propietats. L’objectiu del present projecte de tesi va ser determinar si l’adherència a una Dieta Mediterrània o el consum d’oli d’oliva verge era capaç d’incrementar la funcionalitat de les HDLs o de disminuir l’aterogenicitat de les LDLs en humans. Les mostres del present projecte van procedir de dos assajos clínics aleatoritzats i controlats: l’estudi EUROLIVE (Effects of Olive Oil Consumption on Oxidative Damage in European Populations) i l’estudi PREDIMED (Effects of Mediterranean Diet on the Primary Prevention of Cardiovascular Disease). En ambdós casos, vam aïllar les HDLs i LDLs de diferents sub-mostres de voluntaris i vam realitzar una bateria completa de determinacions relacionades amb la funció d’HDL i l’aterogenicitat de LDL. El consum d’oli d’oliva verge va incrementar la principal funció d’HDL, la capacitat d’eflux de colesterol. Un increment en el contingut de metabòlits dels compostos fenòlics de l’oli d’oliva a les HDLs, així com unes millors composició i grandària, podrien justificar l’anterior millora funcional. Respecte a la Dieta Mediterrània, augmentar l’adherència a aquest patró dietètic va millorar les quatre funcions principals de les HDLs: la capacitat d’eflux de colesterol, el rol de les HDLs en altres punts del transport revers de colesterol, la capacitat antioxidant de les HDLs i la funció vasoprotectora de les lipoproteïnes. Una millora a la oxidació, composició i grandària de les HDLs també podria justificar la millora funcional de les HDLs. A més, el consum d’oli d’oliva verge va disminuir els nivells de LDL i l’aterogenicitat de les mateixes (augmentant la grandària i la resistència davant l’oxidació de les lipoproteïnes). L’adherència a una Dieta Mediterrània també va millorar les característiques pro-aterogèniques de les lipoproteïnes, augmentant la grandària i la resistència a l’oxidació de les lipoproteïnes, disminuint la seva oxidació in vivo, millorant la seva composició i disminuint la seva citotoxicitat en macròfags. En conclusió, el present projecte de tesi demostra que el consum d’oli d’oliva verge o l’adherència a una Dieta Mediterrània millora la funció de les HDLs i l’aterogenicitat de les LDLs en humans en dos assajos clínics aleatoritzats. Els nostres resultats proporcionen dos nous mecanismes per explicar part dels beneficis d’aquestes intervencions dietètiques saludables i recolzen les evidències prèvies que indiquen el rol cardioprotector de l’oli d’oliva verge i la Dieta Mediterrània en humans.

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26

Koska, Juraj, Hussein Yassine, Olgica Trenchevska, Shripad Sinari, Dawn C. Schwenke, Frances T. Yen, Dean Billheimer, Randall W. Nelson, Dobrin Nedelkov, and Peter D. Reaven. "Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes." AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2016. http://hdl.handle.net/10150/614755.

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The apoC-III proteoform containing two sialic acid residues (apoC-III2) has different in vitro effects on lipid metabolism compared with asialylated (apoC-III0) or the most abundant monosialylated (apoC-III1) proteoforms. Cross-sectional and longitudinal associations between plasma apoC-III proteoforms (by mass spectrometric immunoassay) and plasma lipids were tested in two randomized clinical trials: ACT NOW, a study of pioglitazone in subjects with impaired glucose tolerance (n = 531), and RACED (n = 296), a study of intensive glycemic control and atherosclerosis in type 2 diabetes patients. At baseline, higher relative apoC-(I)II2 and apoC-III2/apoC-III1 ratios were associated with lower triglycerides and total cholesterol in both cohorts, and with lower small dense LDL in the RACED. Longitudinally, changes in apoC-III2/apoC-III1 were inversely associated with changes in triglycerides in both cohorts, and with total and small dense LDL in the RACED. apoC-III2/apoC-III1 was also higher in patients treated with PPAR-gamma agonists and was associated with reduced cardiovascular events in the RACED control group. Ex vivo studies of apoC-III complexes with higher apoC-III2/apoC-III1 showed attenuated inhibition of VLDL uptake by HepG2 cells and LPL-mediated lipolysis, providing possible functional explanations for the inverse association between a higher apoC-III2/apoC-III1 and hypertriglyceridemia, proatherogenic plasma lipid profiles, and cardiovascular risk.

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Beck, Caroline. "Assembly and secretion of atherogenic lipoproteins /." Göteborg : The Wallenberg Laboratory for Cardiovascular Research, Dept. of Molecular and Clinical Medicine, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, 2008. http://hdl.handle.net/2077/9855.

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28

Elgallali, Ashraf. "Characterisation of lipoproteins in Staphylococcus aureus." Thesis, University of Salford, 2016. http://usir.salford.ac.uk/38715/.

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The Gram-positive bacterium Staphylococcus aureus is an extremely successful opportunistic bacterium capable of causing a wide range of hospital-acquired and community-acquired infections, and is becoming increasingly virulent and resistant to antibiotics. In order to investigate this pathogen, various methods have been used to analyse the pathogenic behaviour including genomics, transcriptomics and proteomics. S. aureus expresses approximately 55-70 lipoproteins with only about half with known functions. Little is known about the biochemical functions of many individual lipoproteins and their proteomics has not been investigated in detail. Lipoproteins have a broad ranging functionality and perform various roles in bacterial activity and attract a particular interest to investigate their virulence and survival influences in the course of host infection. The initial part of this study was to find out whether the lipoproteins of S. aureus have similar genetic characteristics among all strains. PCR and Quantitative Real-Time PCR experiments were performed to analyse the genetic and the expression levels for some lipoprotein genes. The majority of PCR results showed high similarity in lipoprotein genetic structure among the examined strains. Phylogenetic trees from concatenated lipoprotein genes alignment were generated to represent the lipoprotein genes distribution of S. aureus strains. To identify and characterise proteomic of S. aureus lipoproteins a comprehensive quantitative proteome profiling of S. aureus lipoproteins using gel-free /in-solution trypsin digestion system followed by LC-MS/MS quantification identified 38 lipoproteins that represent two-thirds of the S. aureus MRSA252 lipoprotein. In addition, S. aureus-mediated infections with live C. elegans were performed on solid assays to investigate the host-pathogen relationships. S. aureus MRSA252 exhibited a high level of nematocidal activity with average time for half of the worms to die of ~ 2 d and infected C. elegans showed visible signs of illness. To evaluate lipoprotein transcripts expression level and microbe/host-specific pathogenic factors RNA of both S. aureus and C. elegans were characterised after isolation from the infected C. elegans and subjected to RNA Sequencing, the large-scale data has provided useful information on pathogen and host activities during infection. RNA sequencing analysis showed different types of regulations and interactions of lipoprotein transcripts during host exposures to indicate 3 transcripts significantly were up-regulated and 11 down-regulated. RNA sequencing analysis showed that 62 lipoprotein transcripts were expressed during C. elegans infection model. Proteomic analysis using the application of gel-free proteomic technique identified 38 lipoproteins that were expressed in the non-infection condition representing approx. two-thirds of the S. aureus MRSA252 lipoproteins. The results suggest that some lipoproteins were involved in pathogenesis of C. elegans but their function were not clear. More research is needed for explore the roles of lipoproteins in pathogenesis and the interactions of S. aureus with the host immune responses.

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Merriam, Deborah Lee. "Tyrosyl radical-oxidized high-density lipoproteins." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ28967.pdf.

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30

Ahmad, Feroz. "Lysosomal oxidation of Low Density Lipoproteins." Thesis, University of Reading, 2017. http://centaur.reading.ac.uk/72957/.

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Oxidation of LDL is widely believed to be a key process in the pathogenesis of atherosclerosis. However, LDL oxidation has been shown to be inhibited by interstitial fluid and also large clinical trials have shown no protection by antioxidant. Recent work has shown that LDL can be oxidised by iron within the lysosomes of macrophages. Here, we have explored the possible mechanism by which iron is able to oxidise LDL under lysosomal conditions, and also how lysosomotropic antioxidant, cysteamine is able to prevent it. More recently, it has been shown that human macrophages are able to rapidly phagocytose LDL aggregated by enzymes, such as sphingomyelinase (SMaseLDL) and oxidised it by iron inside lysosomes, which have a pH of about 4.5. Here, the chemical characteristics (lipid hydroperoxides and oxysterols) of SMase-LDL oxidised by inorganic iron at lysosomal pH (4.5) have been determined in vitro and compared to the native LDL. In the lysosomes of macrophages, SMase-LDL increased the intralysosomal lipid peroxidation and ceroid formation which was greatly inhibited by cysteamine. There is good evidence which suggests that lysosomal dysfunction plays an important role in the atherosclerotic plaque development. Here, it is shown that lysosomal oxidation of SMase-LDL in human macrophages can cause lysosomal dysfunction, induce ceroid associated cellular senescence, and increase the expression of inflammatory cytokine like TNF-α. The work here also demonstrates that preventing the lysosomal LDL oxidation, with antioxidants like cysteamine, offers protection against the SMase-LDL induced lysosomal dysfunction.

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Bertato, Marina da Paz. "Cinética plasmática do colesterol livre e do colesterol esterificado e transferência in vitro de lípides para a HDL, utilizando uma nanoemulsão lipídica artificial, em indivíduos com intolerância à glicose." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-24062010-142720/.

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O indivíduo com diabetes mellitus tipo 2 apresenta um risco de 2 a 4 vezes maior de desenvolver doença cardiovascular (DCV) quando comparado ao não-diabético, sendo que este aumento do risco para o desenvolvimento da DCV também é observado quando na intolerância à glicose (IG) que ocorre em fases mais precoces da história natural do diabetes. Atribui-se ser a presença da síndrome metabólica (SM), que ocorre na maioria dos pacientes com DM2 e IG, um fator importante para o desenvolvimento da DCV nestes indivíduos. Dos componentes da SM, inúmeros estudos destacam a dislipidemia como um dos principais fatores para este risco. A dislipidemia comumente encontrada na IG é caracterizada por hipertrigliceridemia, baixo HDL-C e presença de LDL pequena e densa. Entretanto, como a elevação dos níveis séricos do LDL-C associada ao surgimento de aterosclerose prematura em indivíduos não diabéticos na maioria das vezes não é observada em pacientes com IG, questiona-se se outras alterações do metabolismo lipídico, tais como alterações da cinética do colesterol ou a transferência de lípides das lipoproteínas para a HDL, poderiam estar relacionadas ao maior risco cardiovascular nestes pacientes. Estudo prévio, utilizando uma nanoemulsão lipídica artificial de LDL, verificou uma remoção mais rápida do colesterol na forma livre em pacientes normolipidêmicos com doença arterial coronária (DAC) quando comparada com controles. No presente estudo, utilizou-se a nanoemulsão lipídica artificial para avaliar se esses dois processos envolvidos no metabolismo da LDL e da HDL estão alterados em pacientes com intolerância à glicose que os predispõem à DAC, relacionando estes resultados com fatores de risco cardiovasculares, tais como a resistência à insulina, a obesidade e a dislipidemia. Para tanto, foram estudados 14 pacientes com IG e 15 controles, sem manifestação clínica de DCV, que não utilizam antidiabéticos orais e hipolipemiantes, comparados com controles pareados para idade, sexo, raça, IMC, tabagismo, consumo de álcool, prática de atividade física e doenças associadas. Para o estudo cinético, a nanoemulsão marcada foi injetada endovenosamente e amostras de sangue coletadas ao longo de 24h para a determinação da radioatividade, das curvas de decaimento plasmático e da taxa fracional de remoção (TFR) dos lípides marcados a partir de um modelo de análise compartimental. Foi medida a taxa de esterificação do 3Hcolesterol livre da nanoemulsão no plasma e avaliada a transferência in vitro de lípides da nanoemulsão para a fração HDL. A resistência à insulina foi estimada pelo modelo matemático de homeostase glicêmica (HOMA) e a adiposidade abdominal por tomografia computadorizada de abdômen. A concentração plasmática de colesterol total, LDL-C, HDL-C, triglicérides e de apolipoproteínas não diferiu entre os grupos. O perfil antropométrico relacionado ao peso, IMC e circunferência abdominal foi semelhante entre os grupos. O grupo IG apresentou maior concentração de insulina de jejum (p=0,01), menor sensibilidade à insulina (p<0,01) e maior índice de resistência à insulina (p<0,01). A TFR 14C-EC foi similar nos dois grupos, porém a TFR 3H-CL foi mais rápida no grupo IG comparado com controle (p=0,04). A porcentagem de esterificação do 3H-colesterol da nanoemulsão bem como a transferência de lípides da nanoemulsão para a fração HDL foram semelhantes entre os grupos. A remoção mais rápida do 3H-colesterol livre mostra que ocorreu uma dissociação das partículas de colesterol da nanoemulsão lipídica nos pacientes com intolerância à glicose. Essa dissociação do colesterol pode refletir alterações no metabolismo intravascular da lipoproteína LDL, as quais podem favorecer a aterogênese nesses pacientes
Individuals with diabetes mellitus type 2 are 2 to 4 times more susceptible to cardiovascular disease (CVD) than non-diabetic individuals. This increased risk is also observed for glucose intolerance (GI) which appears in the initial stages of diabetes. The presence of the metabolic syndrome (MS), present in most DM2 and GI patients, is also an important factor contributing to the development of CVD in these individuals. Various MS component studies emphasize dyslipidemia as one of the main contributors for this risk factor. The dyslipidemia commonly associated to GI is characterized by hypertriglyciridemia, low HDL-C and the presence of a small and dense LDL. However, since associated LDL-C levels with the development of premature atherosclerosis in non diabetic individuals is for the most part not observed in GI patients, it is questioned whether other lipid metabolism alterations such as cholesterol kinetics or the lipid transfer to HDL could be related to a greater CVD risk in these individuals. A previous study using an artificial LDL nanoemulsion showed a faster removal rate of the free cholesterol in normolipidemic with coronary artery disease (CAD) patients when compared to control individuals. In this study an artificial lipid nanoemulsion was used to evaluate both these processes involved in the metabolism of LDL and HDL which are both altered in patients with GI that expose them to CAD, and relating the results to CVD factors such as insulin resistance, obesity and dyslipidemia. 14 GI and 15 control individuals participated in this study. All without manifestations of CVD, none using any oral antidiabetic medication or hypolipimeants, paired for age, sex, race, BMI, smoking, alcoholic consumption, physical activity and comorbidities. For the kinetic study, a labeled nanoemulsion was interveneously injected and blood samples collected at determined intervals over a 24 hour period to determine the radiactive plasma decay curves and fractional clearance rate (FCR) of the labeled nanoemulsion lipids through a compartmental analysis model. Plasma esterification rate of the 3H-free cholesterol of the nanoemulsion was measured as was the in vitro transfer from the nanoemulsion to HDL fraction. Insulin resistance was obtained by the glycemic homeostasis mathematical model (HOMA) and abdominal adipose by a computerized tomography of the abdomen. No differences were observed for total cholesterol plasmatic concentrations, LDL-C, HDL-C, triglycerides or apolipoproteins between the two groups. The anthropometric profile related to weight, BMI and abdominal circumference was similar for both groups. The GI group presented higher fasting insulin concentration (p=0.01), less insulin sensitivity (p=0.01) and a greater insulin resistance (p=0.01). The TFR 14C-CE was similar in both groups, although the TFR 3H-CL was faster in the GI group compared to the control group (p=0.04). The esterification percentage of the nanoemulsions 3H-colesterol, as well as the lipid transfer from the nanoemulsion to HDL fraction were similar for both groups. The faster 3H-free cholesterol removal shows that a dissociation of the cholesterol particles of the lipidic nanoemulsion occurred in those patients with GI. This dissociation could possibly reflect alterations in the intravascular LDL lipoprotein metabolism which in turn, may favor atherogenesis in these patients

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32

Puig, Gay Natàlia. "Apolipoproteïnes-A en la glomeruloesclerosi focal i segmentària." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/664164.

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La Glomeruloesclerosis Segmentaria i Focal (GESF) és una malaltia renal associada a síndrome nefròtica corticoresistent, el resultat final de la qual és una lesió glomerular que produeix elevada proteïnúria. Segons les causes de la malaltia existeixen varies formes de GESF: les secundaries, d’origen conegut, tals com les mutacions en els gens de proteïnes podocitàries o per hiperfiltració glomerular i la primària o idiopàtica, d’origen desconegut, en la qual es centra aquesta tesis. Tot i la causa desconeguda d’aquesta tipus de GESF varis estudis han arribant a la conclusió que està causada per un o diversos factors plasmàtics encara desconeguts que s’originen fora del ronyó. Un dels principals problemes de GESF és la manca de resposta al tractament amb esteroides, amb progressió freqüent cap a insuficiència renal, diàlisis i finalment el trasplantament renal, que entre el 30-50% dels casos recidiva fins i tot hores desprès de rebre el trasplantament. Això sumat a la dificultat del diagnòstic basat en les característiques clíniques, es a dir, augment de proteïnúria, el qual pot venir per altres causes i detecció de la glomeruloesclerosi segmentària a la biòpsia renal, les quals no solen aparèixer fins al cap d’un mes de l’aparició de proteïnuria, fa que sigui necessari buscar proteïnes útils coma biomarcador que permetin un ràpid diagnòstic així com un pronòstic de la recidiva de GESF Per tot això es va dissenyar un estudi en el qual mitjançant tècniques proteòmiques es pretenia detectar els potencials inductors de la malaltia a més de molècules que poguessin servir com a marcadors pronòstics de recidiva. Hem trobat específicament associades a GESF idiopàtic unes formes d’apolipoproteïnes de HDL: una d'apolipoproteïna A-II monomèrica (ApoA-IIm) en el plasma dels pacients idiopàtics i una d'apolipoproteïna A-I (ApoA-Ib) a l'orina dels pacients trasplantats amb recaiguda de GESF. De l’estudi d’un total de 119 pacients utilitzats en la validació d’ApoA-Ib hem pogut demostrar que ApoA-Ib és un bon biomarcador de recidiva post-trasplantament de GESF amb una sensibilitat i una especificitat del 92.8% i el 98.1% respectivament, un segon estudi va permetre confirmar la utilitat de ApoA-Ib com a biomarcador amb sensibilitat del 93.3%, especificitat del 89.1% , a més de poder ser utilitzat com a biomarcador negatiu (valor predictiu negatiu del 99% en el primer grup i del 97.6% en el segon grup) es a dir l’absència d’ApoA-Ib permet excloure el diagnòstic de recidiva amb una elevada confiança, fins i tot en presencia de proteïnúria severa, complementant el diagnòstic clàssic basat en evidencies histològiques en la biòpsia renal, sobretot en els casos primerencs on les lesions encara no s’han desenvolupat i que per tant el diagnòstic no es clar, a més, té com avantatge que és un biomarcador no invasiu que permet fer mesures fàcils i repetides amb un resultat qualitatiu. També sembla que ApoA-Ib podria ser de gran utilitat en la predicció de la recidiva post-trasplantament de GESF. Hem pogut determinar que ApoA-Ib és en realitat una forma d’apolipoproteïna A-I amb una maduració incompleta i que presenta una part del pro-pèptid unit a ella, donant-li així més pes molecular i un punt isoelèctric més bàsic del que s’esperaria per a l’ApoA-I estàndard. Aquesta forma anòmala d’ApoA-I altera la proporció de les subfraccions de HDL. El paper d’aquesta forma anormal d’Apolipoproteïna A-I en la patogènia del GESF no ha pogut ser evidenciada, encara que s’ha demostrat la seva associació gairebé exclusiva amb les recidives de GESF.
Focal Segmental Glomerulosclerosis (FSGS) is a renal disease characterized by an steroid-resistant nephrotic syndrome and by its frequent evolution to end-stage renal disease. Its incidence has increased the last years, and there is no effective treatment because, in addition to the steroid unresponsiveness, many patients relapse after the kidney transplantation. There is strong evidence that sporadic FSGS (unlike the familial form) is caused by a circulating factor, probably a protein, which increases the glomerular permeability to proteins. Other hypothesis attributes FSGS to the loss of a permeability inhibitor factor. The identification of this factor could allow the design of an efficient therapy for FSGS. A problem of FSGS is the difficulty of the diagnosis based on clinical characteristics: proteinuria increase (which may come from other causes) and the detection of segmental glomeruloesclerosis in the renal biopsy (which does not usually appear until after a month after the appearance of proteinuria). For these reason is necessary to look for useful proteins such as biomarkers that allow a rapid diagnosis as well as a prognosis of recurrence of FSGS. We use proteomic techniques in order to detect the potential inducers of the disease as well as molecules that could be used as prognostic markers of recurrence. We have specifically found some forms of HDL-apolipoproteins associated with idiopathic FSGS: a monomeric apolipoprotein A-II (ApoA-IIm) in the plasma of idiopathic patients and a high molecular weight form of apolipoprotein A-I (ApoA-Ib) in the urine of relapsing FSGS patients. By the study of 119 patients we found that ApoA-Ib is a good biomarker of FSGS recurrence after transplantation with a sensitivity of 92.8% and a specificity of 98.1 %, in addition ApoA-Ib was able to be used as a negative biomarker (negative predictive value of 99%) even in the presence of severe proteinuria, complementing the classical diagnosis based on renal biopsy. We also determine that ApoA-Ib is actually a form of apolipoprotein AI with incomplete maturation and that it presents a part of the pro-peptide attached to it, giving it more molecular weight and a more basic isoelectric point. This anomalous form of ApoA-I alters the proportion of the HDL subfractions. The role of this abnormal form of Apolipoprotein A-I in the pathogenesis of FSGS has not been demonstrated, although it has been demonstrated its exclusive association with FSGS relapses.

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33

Janson, Håkan. "Genetic and biological characterization of protein D a possible virulence factor of Haemophilus influenzae /." Lund : Dept. of Medical Microbiology, Lund University, malmö University Hospital, Lund University, 1995. http://catalog.hathitrust.org/api/volumes/oclc/39793254.html.

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Neves, Vander Jose das 1975. "Efeitos aterogenicos do estresse cronico em aorta toracica de ratos." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288844.

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Orientador: Fernanda Klein Marcondes
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Complicações metabólicas e vasculares podem resultar em aterosclerose, que constitui um grave problema de saúde pública, sendo responsável por cerca da metade da mortalidade relacionada a doenças cardiovasculares no mundo ocidental. Portanto, estudar os fatores de risco associados a esta patologia é fundamental para que se possa estabelecer diretrizes de tratamento e prevenção de distúrbios cardiovasculares. O estresse crônico e a ingestão de dietas hipercalóricas têm sido reconhecidos como fatores de risco para doenças cardiovasculares e para a aterosclerose, por seus efeitos potencialmente deletérios sobre o sistema cardiovascular. O objetivo deste estudo foi avaliar, em ratos, os efeitos aterogênicos do estresse crônico moderado e imprevisível (ECMI), associado ou não à ingestão de dieta hipercalórica, sobre a sensibilidade às catecolaminas em átrio direito e aorta torácica, sobre a morfologia vascular e a influência de lipídios nas alterações funcionais e morfológicas observadas. Buscando avaliar os mecanismos relacionados aos efeitos do estresse crônico, associado ou não, ao consumo de dieta hipercalórica, apresentamos nos capítulos 1 e 2, resultados de estudos in vitro. No capítulo 1, foi mostrado que o ECMI promove supersensibilidade à fenilefrina em aorta torácica isolada de ratos, aumento da espessura do endotélio e da camada média vascular, dislipidemia aterogênica, e elevado índice aterogênico, em relação ao grupo controle, sem alteração da sensibilidade atrial à noradrenalina. Tais alterações parecem estar relacionadas à diminuição da síntese de óxido nítrico endotelial e aumento das concentrações séricas de lipoproteína de baixa densidade (LDL) em ratos submetidos ao ECMI. No capítulo 2 foi mostrado que, em animais não submetidos a estresse, a dieta hipercalórica promoveu aumento da adiposidade e das concentrações séricas de LDL, sem alterações nas concentrações de colesterol total e triglicerídeos, e sem alterações funcionais ou estruturais na aorta torácica. O ECMI promoveu supersensibilidade vascular à fenilefrina, aumento da espessura do endotélio e da camada média vascular e elevação da concentração sérica de LDL em ratos tratados com dieta hipercalórica e em animais tratados com dieta controle, em relação aos respectivos grupos não submetidos a estresse. Além disso, o ECMI promoveu alterações contrárias sobre a adiposidade nos grupos tratados com dieta controle e dieta hipercalórica, diminuindo a adiposidade no primeiro grupo e elevando-a no segundo, em relação aos grupos tratados com a mesma dieta e não submetidos a estresse. Considerando que, apesar de elevadas concentrações de LDL, não houve alterações funcionais ou estruturais na aorta torácica de ratos alimentados com dieta hipercalórica, não submetidos ao ECMI, e que, embora tenha ocorrido maior elevação nas concentrações de LDL em ratos estressados tratados com dieta hipercalórica, as alterações funcionais e morfológicas observadas na aorta torácica e as concentrações de corticosterona deste grupo não diferiram em relação aos animais estressados alimentados com dieta controle. Os resultados apresentados nos capítulos 1 e 2 indicam que o estresse crônico parece potencializar os efeitos aterogênicos das LDL
Abstract: Metabolic and vascular complications can result in atherosclerosis, which constitutes a great problem of public health, associated to approximately half of the deaths related to the cardiovascular illnesses in the occidental world. Therefore to the establishment of guidelines for treatment and prevention of cardiovascular diseases, it is important to study risk factors associated to this pathology. Chronic stress and hypercaloric diet ingestion have been recognized as risk factors for cardiovascular diseases because of its potential deleterious effect on the cardiovascular system. The aim of this work was to evaluate, in rats, the atherogenic effects of chronic mild unpredictable stress (CMS) associated or not to the ingestion of hypercaloric diet on the sensitivity of right atria and thoracic aorta to catecholamines, on the vascular morphology and the influence of lipids in the possible functional and morphological vascular alterations. In order to evaluate the mechanisms related to the effects of chronic stress, associated or not to the consumption of hypercaloric diet, we present in the chapters 1 and 2, results of in vitro studies. In the chapter 1, it was shown that CMS promotes supersensitivity to phenylephrine in thoracic aorta isolated from rats, increases the endothelium and tunica media thickness, atherogenic dyslipidemia, and higher atherogenic index, in comparison with the control group, without alteration in the atrial sensitivity to noradrenaline. These alterations seem to be related to the inhibition of endothelial nitric oxide production and to the increase in the seric levels of low-density lipoprotein (LDL) in rats submitted to the CMS. In chapter 2, it was shown that in non-stressed-animals, hypercaloric diet promoted an increase in the adiposity and seric levels of LDL, without alterations in the levels of total cholesterol, triglicerides and without functional or structural changes in the thoracic aorta. The CMS promoted vascular supersensitivity to phenylephrine, increased the endothelium and tunica media thickness and increased the seric levels of LDL in rats treated with hypercaloric diet and control diet, in comparison with the groups that were not submitted to stress. Furthermore, the CMS promoted contrary alterations on the adiposity in the groups treated with control and hypercaloric diet, decreasing the adiposity in the first one and increasing it in the second group, in comparison with the respective groups treated with the same diet, but not submitted to the CMS. Considering that in spite of high levels of LDL, there were no functional or morphological changes in the thoracic aorta from rats treated with hypercaloric diet and not submitted to the CMS, and that despite the biggest rise in the LDL levels in stressed rats treated with hypercaloric diet, there was no difference between this group and stressed rats treated with control diet in the functional and morphological changes observed in the thoracic aorta as well in the corticosterone levels, the results presented in the chapter 1 and 2, indicate that chronic stress seems to increase the atherogenic effects of the LDL
Mestrado
Fisiologia Oral
Mestre em Odontologia

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35

Gordon, Scott M. "The role of high density lipoprotein compositional and functional heterogeneity in metabolic disease." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353100684.

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Samborski, Rockford William. "A biochemical investigation into the mechanism of hypercatabolism of high density lipoprotein in Tangier disease." Thesis, University of British Columbia, 1987. http://hdl.handle.net/2429/26530.

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This study was designed to investigate the mechanism(s) underlying the hypercatabolism of high density lipoprotein in Tangier disease (TD). Initially, the metabolism of normal HDL incubated in Tangier plasma in vitro was examined. Sufficient normal human HDL was added to TD plasma to raise the concentration of HDL-cholesterol to within normal levels. During incubation the concentration of HDL-cholesterol in the TD plasma fell by up to 50% in a time dependent manner. This was not seen in control samples treated in a similar manner. The loss of HDL-cholesterol in the TD could be completely accounted for by the loss of HDL-cholesteryl ester and was accompanied by a 2.3-fold increase in the concentration of HDL-triglyceride. These observations could not be accounted for by lecithin: cholesterol acytransferase activity, cholesteryl ester hydrolysis, or the triglyceride level in the TD plasma. However, preliminary evidence suggested that the activity of cholesteryl ester transfer protein in TD plasma is responsible for the changes in HDL-lipid composition. The resulting triglyceride-rich, cholesteryl-poor HDL was shown to have a normal affinity for the human skin fibroblast HDL receptor. However, this finding does not exclude other pathways of HDL catabolism that may contribute to the rapid turnover of modified HDL in TD plasma. The metabolism of normal HDL by TD fibroblasts and monocytes in vitro was also studied in an attempt to identify a cellular defect of HDL metabolism in TD. However, both TD fibroblasts and monocytes were normal with respect to their ability to bind/internalize and degrade normal HDL invitro. It is concluded that the hypercatabolism of normal HDL in TD involves alterations of HDL-lipid and protein composition prior to removal from the plasma component. Thus, these studies support the hypothesis that the defect in TD resides in the plasma and not in the cells of these patients.
Medicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate

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37

Myers, Christine Lee. "Detection of oxidation in human serum lipoproteins." Texas A&M University, 2005. http://hdl.handle.net/1969.1/3303.

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A method for the oxidation of lipoproteins in vitro was developed using the free radical initiator, 2,2?-azobis-(2-amidinopropane) dihydrochloride (AAPH). Following in vitro oxidation, the susceptibility to oxidation of the serum samples was studied using density gradient ultracentifugation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Shifts in mean buoyant density of the lipoprotein particles, specifically low density lipoprotein (LDL) and high density lipoprotein (HDL), were observed in the density profile following centrifugation. The degree of shift in the density proved to be proportional to the extent of oxidation. Changes in apolipoproteins were studied with MALDI-TOF-MS. Observed variations in the mass spectra include m/z shifts due to chemical modifications and change in isoform distributions. The oxidation procedure and analysis techniques were applied to a clinical application to study the effects of table grape consumption on lipoprotein susceptibility to oxidation. The main objective of the research, to show feasibility that these methods could be used in a clinical setting, was achieved.

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Mason, Susan Leigh. "Metabolism of triacylglycerol-rich lipoproteins in sheep." Lincoln University, 1991. http://hdl.handle.net/10182/1756.

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This thesis describes two approaches for studying of lipoprotein metabolism in sheep. The first approach involves the assay of lipoprotein lipase (LPL) activity to determine the role of lipoprotein-triacylglycerol fatty acids in fat deposition in sheep. This enzyme is the rate limiting enzyme in the hydrolysis of fatty acids from lipoprotein-triacylglycerol. The second approach was to characterize and quantify in vivo lipoprotein metabolism using iodinated very low density lipoprotein (¹²⁵I-VLDL) and low density lipoprotein (¹³¹I-LDL). Cross-bred lambs were divided into two treatment groups and either weaned early at 5 weeks of age or remained suckling. Lambs were slaughtered at 12 or 23 weeks at which time the body composition and adipose tissue LPL activity were determined. The differences in rearing led to differences in body composition. The suckled lambs were larger and fatter than weaned lambs. The increased fatness in the suckled lambs was associated with increased LPL activity (U/mg protein) in subcutaneous adipose tissue and was reflected in higher LPL activity in post-heparin plasma (PHP) taken 2 days prior to slaughter. The role of insulin in the regulation of LPL activity was investigated by either infusing a subset of the weaned and suckled lambs with insulin for 7 or 18 weeks or using the euglycemic clamp technique to study the effect of short insulin infusions. The long term infusion of insulin had no significant effect on PHP LPL or on adipose tissue LPL (U/g tissue). However, after infusing insulin for 6h at 6.3 mU.kg⁻·⁷⁵.h⁻¹ during the euglycemic clamps, a two fold increase in LPL activity in biopsied subcutaneous adipose tissue was observed. In the second approach, in vivo lipoprotein metabolism was investigated in 4 lambs using apolipoprotein B as a marker. Following the simultaneous injection of ¹²⁵I VLDL and ¹³¹I VLDL, the specific activities of apoB in VLDL, IDL and LDL fractions were determined. ApoB specific activity curves demonstrated that VLDL is metabolised to IDL and subsequently to LDL. The turnover of VLDL-B (3.45mg.d⁻¹.kg⁻¹) and LDL-B (4.8mg.d⁻¹.kg⁻¹) was calculated by fitting the VLDL-¹²⁵I-B and LDL-¹³¹I-B specific activity data to a mono-exponential equation. The metabolism of lipoproteins, inferred from the study of apoB, was shown to be similar in sheep to that reported in other animals although the amount of lipoprotein synthesised was low. A model to describe the kinetics of apoB metabolism in sheep was developed using SAAM. The proposed model features a three pool delipidation chain for VLDL, and subsystems containing two pools for IDL and LDL. IDL may be catabolised to LDL or cleared directly from the plasma. The developed model can now be used to compare the metabolism of lipoproteins in different physiological states and to design new experiments to study lipoprotein metabolism further.

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De, Santis Micaela. "Bacterial lipoproteins: sorting mechanisms and biotechnological applications." Doctoral thesis, Università degli studi di Trento, 2015. https://hdl.handle.net/11572/367625.

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The mechanism responsible for lipoprotein sorting is conserved among bacterial species. However, the final destination of lipoproteins may vary among species. In some species lipoproteins are surface-exposed while in others they are associated to the outer membrane but facing the periplasm. To elucidate whether the difference in lipoprotein location is intrinsic to lipotrotein sequence/structure or rather is due to specific transport systems present in some bacterial species and absent in others lipoproteins were expressed in different species and their compartmentalization analyzed. The data seem to indicate that the destiny of lipoproteins depends upon specific structural signatures but the recognition of such signatures can be species-specific. Interestingly, lipoproteins can be exploited as chaperones to deliver foreign proteins to the outer membrane compartment.

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De, Santis Micaela. "Bacterial lipoproteins: sorting mechanisms and biotechnological applications." Doctoral thesis, University of Trento, 2015. http://eprints-phd.biblio.unitn.it/1411/1/Micaela_De_Santis_Ph.D_thesis.pdf.

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The mechanism responsible for lipoprotein sorting is conserved among bacterial species. However, the final destination of lipoproteins may vary among species. In some species lipoproteins are surface-exposed while in others they are associated to the outer membrane but facing the periplasm. To elucidate whether the difference in lipoprotein location is intrinsic to lipotrotein sequence/structure or rather is due to specific transport systems present in some bacterial species and absent in others lipoproteins were expressed in different species and their compartmentalization analyzed. The data seem to indicate that the destiny of lipoproteins depends upon specific structural signatures but the recognition of such signatures can be species-specific. Interestingly, lipoproteins can be exploited as chaperones to deliver foreign proteins to the outer membrane compartment.

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Camerotto, C. "OBESITY AND METABOLIC SYNDROME: PLASMA LIPOPROTEINS ALTERATIONS." Doctoral thesis, Università degli Studi di Milano, 2011. http://hdl.handle.net/2434/151781.

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Obesity, especially if associated with metabolic syndrome, promotes oxidative stress, a low grade chronic inflammatory state, and modify the composition and function of plasma lipoproteins. Oxidative damage to lipoproteins not only make LDL atherogenic but can also alter HDL reducing their anti-atherogenic properties. The possibility of monitoring the lipid peroxidation of the individual regions of LDL and HDL could lead to more detailed information on the molecular mechanisms that are the basis of the increased risk of cardiovascular diseases observed in obesity and metabolic syndrome. The object of this study was to investigate the susceptibility to peroxidation of plasma and of the hydrophobic core and the surrounding envelope of LDL and HDL in obese male (BMI between 25 and 35 Kg mq) with (SM, n=20)) or without (OB, n =40) metabolic syndrome. The susceptibility of plasma to peroxidation was higher in SM and OB than in normo-weight controls (CT, n=60), but not significant differences were observed between these two obese groups. Also the susceptibility to peroxidation of isolated LDL and HDL was higher in both obese groups than in CT. LDL and HDL in SM presented an higher content of triacylglicerols than the corresponding HDL of OB. Moreover, the hydrophobic core of HDL showed a risk of peroxidation significantly higher in SM than in OB. This last parameter was inversely correlated with the waist to hip ratio, an index of visceral obesity. This last evidence seems to indicate that the increase of inflammation typical of the visceral adipose tissue could be one of the major causes of the higher susceptibility to peroxidation found in the hydrophobic core of HDL. The evaluation of the susceptibility to peroxidation of the core and the envelope of LDL and HDL might contribute to the identification of a subset of patients at increased risk of metabolic and cardiovascular complications. Future “ad hoc” randomized clinical trials should be designed to address the effects of weight reduction and /or different diet and/or nutritional supplementation on these parameters.

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Júnior, Antonio Carlos de Arruda Leite. "Avaliação de aspectos funcionais da lipoproteína de alta densidade (HDL) e suas subfrações em pacientes com doença arterial coronária." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-01072015-103450/.

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Estudos clínicos e epidemiológicos indicam que baixas concentrações plasmáticas da lipoproteína de alta densidade (HDL) estão forte e independentemente associadas a uma maior incidência de doença arterial coronária (DAC). Entretanto, o insucesso dos agentes que são capazes de aumentar a concentração de HDL-C sugere que a funcionalidade da HDL pode representar um alvo terapêutico mais apropriado. Para a avaliação de um dos aspectos funcionais da HDL, o presente trabalho descreve o desenvolvimento de um método de grande praticidade que permite uma visão integrada de uma etapa fundamental do metabolismo que é a transferência de lípides entre as diferentes classes de lipoproteínas. A avaliação deste fenômeno nas subfrações de HDL, aspecto ainda não explorado, poderá fornecer novas informações a respeito da fisiopatologia da DAC. O método descrito no presente trabalho permite a avaliação da transferência simultânea das quatro principais classes lipídicas doadas por uma nanoemulsão semelhante à LDL para a HDL3. Foi realizada análise dos possíveis interferentes neste método. Verificou-se que a elevação da temperatura de 0 a 40 °C resultou em aumento progressivo na transferência de todos os lipídeos para a HDL3. A variação de pH entre 6,5 e 8,5 e o aumento na concentração de albumina não alteraram os valores de transferência. O aumento no tempo de incubação acima de 60 minutos promoveu diminuição na transferência de colesterol esterificado para a HDL3 e aumento na transferência de fosfolipídeos. O método apresentou boa precisão intra e inter-ensaio, sendo o coeficiente de variação menor que 5% para todos os lipídeos. A porcentagem média de transferência de colesterol livre, fosfolipídeos, triacilglicerol e colesterol em 45 invíduos saudáveis foi de respectivamente de 1,1±0,06; 13,5±0,15; 2±0,05 e 0,84±0,04% e em 45 portadores de doença arterial coronária foi respectimente 1,0±0,04; 15,8±0,44; 1,77±0,04 e 1,0±0,06%. Não houve diferença nos valores de idade, IMC, colesterol total, HDL-C, LDL-C, triacilglicerol, apo A-1, apo B, CETP, PLTP e LCAT, mas os indivíduos portadores de doença arterial coronária apresentaram valores maiores de colesterol livre e colesterol total em relação aos indivíduos saudáveis. O método desenvolvido no presente estudo é prático, preciso e de potencial relevância como ferramenta no estudo dos distúrbios de função da HDL..
Clinical and epidemiological studies show that low concentrations of high density lipoproteins (HDL) are strongly and independently associated to an increased incidence of coronary artery disease (CAD). However, the lack of success of some drugs developed to increase HDL cholesterol concentrations (HDL-C) suggests that the functional aspects of HDL may represent a more appropriate therapeutic target. To study one of the functional aspects of HDL, the present work describes the development of a practical method that provides an integrated view of a fundamental step of lipid metabolism, namely, the lipid transfer among different lipoprotein classes. This phenomenon in the HDL subfractions is yet unexplored, and could provide new insights on the pathophysiology of CAD. The method described here allows the measurement of the ability of HDL3 to receive the major lipid classes from a radioactively labeled nanoparticle that resemble LDL. The possible interfering factors at the lipid transfer to HDL3 were studied. The increase in the assay temperature from 0 to 40 °C results in a progressive increase in the net transfer of all lipids to HDL3. The increase in incubation time above 60 minutes resulted in a reduced transfer of cholesterol esters to HDL3 with a concomitant increase in the transfer of phospholipids to the latter. The method presented adequate intra and inter-assay precision, with a coefficient of variation smaller than 5% for all lipids. The average percentage of free cholesterol, phospholipids, triacilglycerol an cholesterol transfer to HDL3 was respectively of 1,1±0,06; 13,5±0,15; 2±0,05 e 0,84±0,04% in 45 healthy individuals and 1,0±0,04; 15,8±0,44; 1,77±0,04 e 1,0±0,06% in 45 CAD patients. There was no difference in the age, BMI, total cholesterol, HDL-C, LDL-C, triacilglycerol, apo A-1, apo B, CETP, PLTP and LCAT but the CAD patients had higher levels of total cholesterol and free cholesterol. The method described here is practical, precise and potentially relevant as a tool to study HDL function.

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Pinto, Paula Ramos. "Treinamento físico aeróbio em camundongos selvagens e transgênicos para CETP não altera a remoção de colesterol celular e a expressão de genes envolvidos no fluxo de lípides em macrófagos e arco aórtico." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-23092015-110341/.

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O exercício físico regular contribui para prevenção e redução da aterosclerose, em grande parte, por melhorar o perfil lipídico e o transporte reverso de colesterol (TRC). O TRC é um sistema antiaterogênico que promove a remoção do excesso de colesterol de macrófagos pelas apo A-I e HDL e seu transporte ao fígado, com eliminação de colesterol na bile e fezes. Em camundongos selvagens e transgênicos para proteína de transferência de colesterol esterificado (CETP-tg), o treinamento físico aumentou a transferência de colesterol radioativo de macrófagos para o plasma, fígado e fezes e o conteúdo dos receptores B-E e SR-BI no fígado. Em leucócitos, hepatócitos e enterócitos, o exercício físico aumentou a expressão do receptor de HDL, ABCA-1. Entretanto, não é claro se o exercício físico modula o fluxo de lípides em macrófagos, o que seria determinante para a primeira etapa do TRC. Assim sendo, avaliou-se, em camundongos selvagens e CETP-tg, o efeito do treinamento físico aeróbio sobre: 1) a expressão de genes envolvidos no fluxo de lípides, modulação da resposta inflamatória, vasodilatadora e antioxidante: Pparg (PPAR?), Nr1h3 (LXRalfa), Nr1h2 (LXRbeta), Abca1 (ABCA-1), Abcg1 (ABCG-1), Scarb1 (SR-BI), Cd36 (CD-36), Olr1 (LOX-1), Ccl2 (MCP-1), Tnf (TNFalfa), Il6 (IL-6), Il10 (IL10), Nos3 (eNOS) e Cat (Catalase) na parede arterial e em macrófagos peritoneais; 2) o efluxo de 14C-colesterol de macrófagos peritoneais para HDL2 e apo A-I e 3) a captação de 3H-colesteril oleoil éter-LDL (3H-COE-LDL) acetilada por macrófagos peritoneais. Camundongos machos com 12 semanas de idade, recebendo dieta padrão e água ad libitum, foram aleatoriamente divididos em grupo sedentário e treinado. O treinamento físico foi realizado em esteira, 15m/min, 30 min/dia, 5 vezes/semana, durante 6 semanas. Arco aórtico e macrófagos da cavidade peritoneal foram isolados dos animais sedentários e treinados, imediatamente (0 h) e após 48 h da última sessão de exercício. A expressão de genes foi avaliada por RT-PCR e o efluxo de colesterol, por meio da sobrecarga de macrófagos peritoneais com LDL acetilada e 14C-colesterol, seguindo-se incubação com apo A-I ou HDL2. A captação de LDL foi determinada pela incubação de macrófagos com 3H-COE-LDL acetilada. Não foram observadas alterações sistemáticas na expressão de genes envolvidos no fluxo de lípides em macrófagos e na aorta comparando-se animais sedentários e treinados, selvagens ou CETP-tg. De modo semelhante, não houve diferença no efluxo de colesterol celular e na captação de LDL. Em conclusão, não foram evidenciadas alterações em macrófagos peritoneais e na parede arterial frente ao treinamento físico aeróbio que possam contribuir para o TRC em modelo experimental de camundongos não dislipidêmicos, sem intervenção farmacológica ou alimentar. Sendo assim, o efeito do treinamento físico na melhora do transporte reverso de colesterol, observado em estudos anteriores, deve ser consequente à sua ação sistêmica sobre mediadores deste transporte e expressão de receptores no fígado e intestino
Regular physical exercise prevents and reduces atherosclerosis mainly by improving lipid profile and reverse cholesterol transport (RCT). RCT is an antiatherogenic system that promotes excess cholesterol removal from macrophages by apo A-I and HDL and its transport to the liver. Then, cholesterol can be secreted into bile and excreted in feces. In wild type and cholesteryl ester transfer protein transgenic (CETP-tg) mice exercise training increased the transfer of 14C-cholesterol from macrophages to plasma, liver and feces and elevated SR-BI and B-E receptor content in the liver. In leucocytes, hepatocytes and enterocytes, physical exercise increased mRNA of HDL receptor, ABCA-1. Nonetheless, it is not clear if exercise can modulate lipid flux in macrophages that can be important for the first phase of the RCT. It was analyzed in wild type and CETP-tg mice the effect of aerobic exercise training in: 1) the expression of genes involved in lipid flux, inflammation, oxidation and vasodilation: Pparg (PPAR?), Nr1h3 (LXRalfa), Nr1h2 (LXRbeta), Abca1 (ABCA-1), Abcg1 (ABCG-1), Scarb1 (SR-BI), Cd36 (CD-36), Olr1 (LOX-1), Ccl2 (MCP-1), Tnf (TNFalfa), Il6 (IL-6), Il10 (IL10), Nos3 (eNOS) and Cat (Catalase) in arterial wall and peritoneal macrophages; 2) the apo A-I and HDL2-mediated cholesterol efflux from macrophages and 3) the uptake of 3H-cholesteryl oleoyl ether- acetylated LDL (3H-COE-LDL) by macrophages. Twelve week old male mice fed a chow diet and water ad libitum were randomly assigned to sedentary and trained groups. Exercise training was performed in a treadmill (15m/min, 30 min/day, 5 times/week, during 6 weeks). Aortic arch and peritoneal macrophages were isolated from sedentary and trained animals immediately (time 0) and 48 h after the last exercise session. Gene expression was analyzed by RT-PCR and cholesterol efflux mediated by apo A-I or HDL2 after macrophage overloading with acetylated LDL and 14C-cholesterol. LDL uptake by macrophages was determined by incubation with 3H-COE-acetylated LDL. There were no systematic changes in the expression of macrophages and aortic genes comparing sedentary and trained wild type or CETP-tg mice. Similarly, there were no changes in cholesterol efflux and LDL uptake by macrophages. In conclusion, it was not found alteration in gene expression and cholesterol flux in macrophages and arterial wall that can contribute to the RCT in experimental model of non-dyslipidemic mice without pharmacological or dietary interventions. Therefore, the benefits of aerobic training in improving RCT, observed in previews studies, should be consequent to its systemic action on mediators of this transport and on the expression of hepatic and intestinal receptors

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Pastori, Waleska Tobo. "Suplementação com óleo de soja para eqüinos." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/10/10135/tde-22022008-160519/.

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Em um delineamento em Quadrado Latino 4X4 balanceado, foram utilizados quatro potros, filhos do mesmo garanhão, com idade entre 10 e 12 meses e peso médio de 270 kg (dp ± 9,80 Kg). Foram analisados os efeitos, por regressão simples polinomial, da inclusão dos níveis de 5, 10, 15 e 20 % de óleo de soja, no concentrado, sobre aceitabilidade, coeficiente de digestibilidade aparente da matéria seca (CDAMS), matéria orgânica (CDAMO), proteína bruta (CDAPB), extrato etéreo (CDAEE), fibra insolúvel em detergente neutro (CDAFDN), em detergente ácido (CDAFDA) e sobre a concentração plasmática de colesterol total (COL) e suas frações nas lipoproteína de densidade muito baixa (VLDL-C), lipoproteína de densidade baixa (LDL-C), lipoproteína de densidade alta (HDL-C) e triglicérides totais (TRG). O aumento do nível de inclusão de óleo afetou (p<0,05) o CDAMO, CDAFDN e CDAFDA, apresentando uma resposta quadrática, com diminuição da digestibilidade após o valor esperado de 10,7%, 9,5% e 10,5% EE na dieta, respectivamente. Observou-se resposta linear (p<0,05) dos tratamentos sobre a concentração plasmática de colesterol e LDL-C, apresentando diminuição 0,65 mg/dL de colesterol e 0,58 mg/dL de LDL-C para cada 1% de aumento no EE no concentrado. A inclusão de óleo de soja afetou a digestibilidade da dieta, principalmente na fração parede celular e diminuiu a concentração plasmática de colesterol e HDL-C.
In a balanced 4x4 Latin Square design, 04 foals from the same stallion were used. They aged between 10 and 12 months and their average weight was 270±9.80 kg. The effects of soybean oil inclusion at the concentrated on acceptability, coefficient of apparent digestibility to dry matter (CADAMS), organic matter (CADOM), crude protein (CADCP), ethereal extract (CADEE), neutral detergent fiber (CADNDF), acid detergent (CADADF) and the plasma concentrations of total cholesterol (COL) and the fractions in Very Low Density Lipoprotein (VLDL - C), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C) and total triglycerides (TRG), at the following levels of 5, 10, 15 and 20%, were analyzed by simple polynomial regression. Increase in the level of oil inclusion affected (P<0.05) CADOM, CADNDF and CADADF, showing a quadratic response. For those parameters, digestibility was decreased after inclusion of 10.7%, 9.5% and 10.5 of EE% in the diet, respectively. There was a linear response (P<0.05) to the treatments on the cholesterol plasma concentration and LDL-C; each 1% of increase in EE on the diet caused a decreased of 0.65 mg/dL on cholesterol and 0.58 mg / dL on LDL-C. The inclusion of soybean oil affected the digestibility of the diet, mainly on cell wall fraction, and decreased the concentration of plasma cholesterol and HDL-C.

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Gonzaga, Iaçanã Valente Ferreira. "Suplementação com óleo de arroz semi-refinado com alto teor de gama-orizanol na dieta de garanhões." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/10/10135/tde-23012009-135008/.

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Durante 60 dias foram utilizados seis garanhões de raças variadas, com peso médio inicial de 472,67±90,48 kg, alimentados duas vezes ao dia com dietas compostas por feno de Tifton (Cynodon dactylon) e concentrado comercial, suplementadas com 300 mL de óleo vegetal (óleo de arroz ou óleo de soja), além de sal mineralizado e água ad libitum. Foi avaliado o efeito da suplementação com óleo de arroz semi-refinado com alto teor de gama-orizanol sobre a aceitabilidade da dieta, ganho de peso, escore corporal, lipídeos plasmáticos, digestibilidade aparente dos nutrientes da dieta (Matéria Seca MS, Matéria Orgânica MO, Proteína Bruta PB, Fibra em Detergente Neutro FDN e Fibra em Detergente Ácido FDA), além da qualidade espermática e testosterona plasmática. Para tal observação, foram colhidas amostras sangüíneas com 0, 15, 30, 45 e 60 dias após o início do tratamento para mensuração das concentrações plasmáticas de testosterona, triglicérides, colesterol total e suas frações, tais como lipoproteína de densidade muito baixa (VLDL-C), lipoproteína de densidade baixa (LDL-C) e lipoproteína de densidade alta (HDL-C). Para avaliação da digestibilidade aparente dos nutrientes da dieta, os animais passaram por três dias de colheita total de fezes. Para avaliação da qualidade espermática, os garanhões passaram por colheita seminal com 0, 15, 30, 45 e 60 dias do tratamento. O delineamento experimental foi inteiramente casualisado com medidas repetidas no tempo e as médias foram comparadas considerando-se o nível de 5% de significância. Os valores médios obtidos para a digestibilidade aparente da MS, MO, EE, FDN e FDA foram respectivamente 64,34; 68,03; 71,95; 83,37; 62,15 e 55,05% para o tratamento com óleo de soja, e 58,97; 62,61; 66,96; 81,94; 54,85 e 45,87% para o tratamento com óleo de arroz. Não houve diferença (p < 0,05) em relação à digestibilidade aparente dos nutrientes da dieta para os tratamentos propostos. Os valores médios para testosterona, colesterol total, HDL-C, LDL-C, VLDL-C e triglicérides foram respectivamente 75,93 ng/dL; 92,73; 61,47; 26,99 e 4,28 mg/dL para o tratamento com óleo de soja; e de 62,13 ng/dL; 110,20; 66,73; 38,44 e 5,02 mg/dL para o tratamento com óleo de arroz. Em relação à qualidade espermática, também não se observou (p < 0,05), e os valores médios para volume, motilidade, vigor, concentração, defeitos maiores, defeitos menores e defeitos totais, foram respectivamente, de 71,87 mL; 69 %; 2,63; 123 x 106 espermatozóides/mL; 17,73%; 4,60% e 22,33 % para o tratamento com óleo de soja, e de 78,67 mL; 70,67%; 2,93; 115,67 x 106 espermatozóides/mL; 17,96%; 6,03% e 22,63% para o tratamento com óleo de arroz. Podemos concluir que a suplementação da dieta com óleo de arroz semi-refinado, com alto teor de gama-orizanol, proporciona melhora do ganho de peso e do escore corporal, não afeta a qualidade espermática ou a concentração plasmática de testosterona, VLDL-C, HDL-C e triglicérides, porém, eleva as concentrações plasmáticas de colesterol total e de LDL-C.
Using up six stallions of various breeds during 60 days, with initial average weight of 472,67 ¬± 90,48 kg, fed twice a day with a diet consisting of Tifton hay (Cynodon dactylon) and commercial concentrate, supplemented with 300 mL. of a vegetable oil (rice bran or soybean), moreover mineralized salt and ad libitum water. The experiment evaluated the effect of the supplementation of diet with rice bran oil, with high level of gamma-oryzanol, about acceptability of the diets, weight gain, body score, levels of plasmatic lipids, apparent digestibility of nutrients of the diets (dry matter - DM, organic matter - OM, crude protein - CP, ether extract - EE, neutral detergent fiber - NDF and acid detergent fiber ADF), and spermatic quality and plasmatic testosterone. Blood samples were also held with 0, 15, 30, 45 and 60 days after starting treatment, for analysis of the values of testosterone, triglycerides, total cholesterol and its fractions (HDL-C, LDL-C and VLDL-C). To evaluation of the apparent digestibility of the nutrients of the diet, the animals had passed for three days of total fecal collection. To evaluation of the sperm quality, the sires had passed for seminal collection with 0, 15, 30, 45 and 60 days of the treatment. It was used completely randomized design for repeated measures design with repeated measures over time and the means were compared under 5 % significance level. The gotten average values for the apparent digestibility of the DM, OM, CP, EE, NDF and ADF were respectively 64,34; 68,03; 71,95; 83,37; 62,15 and 55.05 % for the treatment with soybean oil, and 58,97; 62,61; 66,96; 81,94; 54,85 and 45.87 % for the treatment with rice bran oil. There was no statistical difference (p < 0,05) from the apparent digestibility of nutrients of the diet. The average values for testosterone, total cholesterol, HDL-C, LDL-C, VLDL-C and triglycerides had been respectively 75,93 ng/dL; 92,73; 61,47; 26,99 and 4,28 mg/dL for the treatment with soy oil; and of 62,13 ng/dL; 110,20; 66,73; 38,44 and 5,02 mg/dL for the treatment with rice bran oil. In relation to the spermatic quality, also did not have difference (p < 0,05), and the average values for volume, motility, vigor, concentration, defects, lesser defects and total defects, had been respectively, of 71,87 mL; 69%; 2,63; 123 x 106 sptz/mL; 17.73%; 4.60% and 22.33% for the treatment with soybean oil, and 78,67 mL; 70.67%; 2,93; 115,67 x 106sptz/mL; 17.96%; 6.03% and 22,63% for the treatment with rice bran oil. The supplementation of diet with semi-refined rice bran oil, with high level of gamma-oryzanol, provided better weight gain and improves the body score, do not affect the sperm quality or plasmatic levels of testosterone, VLDL-C, HDL-C and triglycerides, however, it increase plasmatic levels of total cholesterol and LDL-C.

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Pereira, Priscila Romero Mazzini. "Caracterização imunogênica e funcional de duas lipoproteínas preditas de Leptospira interrogans expressas em Escherichia coli." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-23052017-141254/.

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A leptospirose é a zoonose mais disseminada no mundo e uma das principais causas de perda econômica no agronegócio. O estudo de novos antígenos de superfície de Leptospira interrogans, é intrigante e pode fornecer conhecimento na interação inicial patógeno-hospedeiro. Os genes LIC13059 e LIC10879, escolhidos por bioinformática, com predição de localização na superfície celular, foram clonados e as proteínas recombinantes expressas em E. coli, para avaliar a interação com componentes do hospedeiro. Após purificação, as proteínas encontravam-se estruturadas e foram reconhecidas por soro de indivíduos infectados. As proteínas recombinantes interagem com plasminogênio, fibrinogênio e laminina. rLIC13059, nomeada Lsa25.6, quando ligada ao fibrinogênio é capaz de inibir a formação de coágulo de fibrina e rLIC10879, nomeada Lsa16, interage com e-caderina, sugerido envolvimento na cascata de coagulação e ligação com o hospedeiro, respectivamente. O plasminogênio ligado às proteínas é convertido em plasmina, o que poderia ajudar a penetração bacteriana no hospedeiro.
Leptospirosis is the most widespread zoonosis and also a major cause of economic loss in animal production worldwide. The study of new surface antigens of Leptospira interrogans is intriguing and may shed light into the initial pathogen-host interactions. We set out to study two novel coding sequences LIC13059 and LIC10879 predicted to be located at the cell surface. The genes were cloned and the recombinant proteins were expressed in E. coli. The purified recombinant proteins presented secondary structures, and interacted with plasminogen, fibrinogen and laminin human components. rLIC13059, named Lsa25.6, when bound to fibrinogen was capable of inhibiting the formation of fibrin clot, while rLIC10879, named Lsa16, interacted with e-cadherin, a mammalian cell receptor, suggesting participation in coagulation pathway and host-cell binding, respectively. The plasminogen captured by both recombinant proteins could be converted into plasmin, a mechanism that could help bacterial penetration in the host.

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Steiner, Marcelo Luis. "Avaliação comparativa da eficácia da terapia de reposição hormonal de baixa dose isolada ou associada à sinvastatina no perfil lipídico e lipoprotéico em mulheres sintomáticas e dislipidêmicas na pós-menopausa /." Botucatu : [s.n.], 2011. http://hdl.handle.net/11449/106365.

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Orientador: César Eduardo Fernades
Banca: Eliana Petri Nahas
Banca: Paulo Traiman
Banca: Luciano de Melo Pompei
Banca: Paula Andrea de Albuquerque Salles Navarro
Resumo: Avaliar comparativamente a eficácia da terapêutica de reposição hormonal (TRH) de baixa dose isolada ou associada à sinvastatina no comportamento de marcadores de risco cardiovasculares e do perfil lipídico e lipoprotéico em mulheres sintomáticas e com dislipidemia na pós-menopausa. Duzentas e quarenta e duas mulheres na pós-menopausa, sintomáticas e com dislipidemia foram randomizadas em três grupos de tratamento: A) estradiol (E2) 1mg/acetato de noretisterona (NETA) 0,5mg [E2/NETA] + sinvastativa 20mg; B) E2/NETA + placebo; e C) sinvastatina 20mg + placebo. A eficácia de cada tratamento foi avaliada pela melhora do perfil lipídico e lipoprotéico e dos sintomas climatéricos ao final de 16 semanas de tratamento. O colesterol total, o LDL-C, o colesterol não-HDL e a Apo B diminuíram de forma significativa (p<0,0001) ao final de 16 semanas no grupo que utilizou E2/NETA + sinvastatina e naquele tratado com sinvastatina + placebo. A relação Apo B/Apo A1 também apresentou redução significativa nestes dois grupos (p<0,0001 e p=0,0026 respectivamente). A Apo A1 diminuiu apenas no grupo que recebeu E2/NETA + sinvastatina (p=0,0055). O grupo E2/NETA + placebo não apresentou alterações significativas no perfil lipídico e lipoprotéico entre as visitas basal e final. Aquele que utilizou E2/NETA + sinvastatina apresentou redução significativa do HDL-C e da Apo A1 quando comparado às usuárias de sinvastatina + placebo (p=0,0233 e p=0,0231 respectivamente). No alívio dos sintomas climatéricos, os grupos que utilizaram E2/NETA foram superiores a sinvastatina + placebo. Em mulheres na pós-menopausa com dislipidemia, a associação de E2/NETA em baixa dose com sinvastatina aliviou os sintomas climatéricos de forma semelhante à observada com a E2/NETA isolada e melhorou o perfil lipídico e lipoprotéico de modo semelhante ao uso isolado da sinvastatina. O uso de E2/NETA sem ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: To evaluate low-dose hormone therapy (HT) + simvastatin for vasomotor symptoms and cardiovascular risk markers. Symptomatic postmenopausal women (n=242) with dyslipidemia were randomized to one of three treatment groups: A) 1mg estradiol/0.5mg norethisterone acetate (E2/NETA) + 20mg simvastatin; B) E2/NETA + placebo; or C) 20mg simvastatin + placebo. Lipid and lipoprotein profiles and menopausal symptoms were evaluated after 16 weeks. Total cholesterol, LDL cholesterol, non-HDL cholesterol and Apo-B decreased (p<0.0001) in groups A and C, as did Apo-B/Apo-A1 (p<0.0001 and p=0.0026, respectively). Apo-A1 decreased only in group A (p=0.0055). HDL cholesterol and Apo-A1 were lower in A than C (p=0.0233 and p=0.0231, respectively). Relief of menopausal symptoms was better in A and B compared to C. HT + simvastatin were effective for the treatment of symptomatic postmenopausal women and improved the lipid profile similar to simvastatin alone. It also delivered an improvement in the simultaneous treatment of menopausal symptoms and dyslipidemia
Doutor

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Zago, Vanessa Helena de Souza 1984. "Estudo molecular dos genes ABCA1, ABCG1, ABCG5, ABCG8 e SCARB1 em amostra populacional brasileira assintomática." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312594.

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Orientadores: Eliana Cotta de Faria, Helena Coutinho Franco de Oliveira, Daniel Zanetti Scherrer
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-26T20:49:38Z (GMT). No. of bitstreams: 1 Zago_VanessaHelenadeSouza_D.pdf: 5059555 bytes, checksum: 854d9d1d1674a14d2ebcf5798acc31b3 (MD5) Previous issue date: 2015
Resumo: Dado o importante papel desempenhado pelos transportadores ATP binding cassete A1 (ABCA1), G1 (ABCG1), G5 (ABCG5), G8 (ABCG8) e pelo scavenger receptor class B type I (SR-BI) para a homeostase corpórea de colesterol e desenvolvimento da aterosclerose, este trabalho se propôs a: (i) investigar a relação dos polimorfismos rs2275543 (ABCA1), rs1893590 (ABCG1), rs6720173 (ABCG5), rs6544718 (ABCG8) e rs5888 (SCARB1) com gênero, idade e índice de massa corpórea (IMC) e suas interações sobre variáveis clínicas e bioquímicas (n=654); (ii) determinar a repercussão destes polimorfismos sobre os parâmetros estudados na população total e de forma gênero-específica (n=590) e (iii) avaliar se os miRNAs hsa-miR-33a e hsa-miR-128a são diferencialmente expressos em um subgrupo da população (n=51) e averiguar sua associação com as concentrações plasmáticas do colesterol da lipoproteína de alta densidade (HDL-C), aterosclerose subclínica e expressão de ABCA1, ABCG1 e SCARB1. Para tanto, foram selecionados voluntários normolipidêmicos e assintomáticos, de ambos os gêneros, com idade entre 20 e 75 anos. Dados clínicos e antropométricos foram obtidos, assim como sangue venoso periférico para as determinações bioquímicas e extração de DNA e RNA. O subgrupo de 51 voluntários foi classificado de acordo com HDL-C (mg/dL) em hipoalfalipoproteinêmicos (hipo, HDL-C?39), hiperalfalipoproteinêmicos (hiper, HDL-C?68) e controles (CTL, HDL-C?40<68) e determinadas a espessura íntimo-medial das artérias carótidas e proteínas relacionadas ao metabolismo de HDL. Determinamos que o rs1893590 interage com a idade e o IMC, modulando as concentrações de HDL-C, bem como o tamanho e volume da partícula, sugerindo que este pode modificar seu metabolismo e composição. Nas análises comparativas o rs2275543 apresentou efeitos diferentes, porém benéficos para ambos os gêneros; adicionalmente, o rs6720173 determinou um fenótipo lipoproteico proaterogênico no gênero masculino, enquanto as variantes rs5888 e rs6544718 repercutiram sobre marcadores de adiposidade no gênero feminino. A análise dos cinco polimorfismos nesta população fornece evidências de que estes atuam em diferentes vias do metabolismo lipoproteico, e tem na maioria dos casos características gênero-específicas. Adicionalmente, a avaliação da expressão de hsa-miR-33a, hsa-miR-128a, ABCA1, ABCG1 e SCARB1 revelou que os indivíduos hiper apresentam um aumento da expressão de ABCA1 e ABCG1 em relação ao grupo CTL, somado a uma redução de 72% na expressão do hsa-miR-33a; em conjunto, estes resultados indicam um potencial papel regulatório deste miRNA em indivíduos assintomáticos, possivelmente contribuindo para o aumento do efluxo e do transporte reverso de colesterol
Abstract: Given the important role played by ATP binding cassete transporters A1 (ABCA1), G1 (ABCG1), G5 (ABCG5), G8 (ABCG8) and by scavenger receptor class B type I (SR-BI) on body cholesterol homeostasis and atherosclerosis development, this study proposes to: (i) investigate the relationship of polymorphisms rs2275543 (ABCA1), rs1893590 (ABCG1), rs6720173 (ABCG5), rs6544718 (ABCG8) e rs5888 (SCARB1) with gender, age and body mass index (BMI) and its interactions with clinical and biochemical variables (n=654); (ii) determine the effects of these polymorphisms on the studied parameters in the total population and in a gender-specific manner (n=590) and (iii) evaluate if miRNAs hsa-miR-33a e hsa-miR-128a are differentially expressed in a subgroup of the population (n=51) and verify its association with plasma levels of high-density lipoprotein cholesterol (HDL-C), subclinical atherosclerosis plus ABCA1, ABCG1 and SCARB1 expression. Thus, normolipidemic and asymptomatic volunteers from both genders, with ages ranging from 20 to 75 years were selected. Clinical and anthropometric data were obtained, as well as peripheral venous blood for biochemical determinations plus DNA and RNA extraction. The subgroup of 51 individuals was classified according HDL-C (mg/dL) in hypoalphalipoproteinemics (hypo, HDL-C?39), hyperalphalipoproteinemics (hyper, HDL-C?68) and controls (CTL, HDL-C?40<68); then, were determinated the carotid intima-media thickness and proteins related to HDL metabolism. The polymorphism rs1893590 interacts with age and BMI, modulating HDL-C levels as well as the particle size and volume, suggesting its role on HDL metabolism and composition. Comparative analysis demonstrated that rs2275543 has different, but beneficial repercussions in both genders; furthermore, rs6720173 determines a pro-atherogenic lipoprotein profile in males, while the variants rs5888 and rs6544718 affect positively adiposity markers in females. The analyses of the five studied polymorphism in this population provide evidences of its role in several pathways of lipoproteins metabolism, in most cases in a gender-specific manner. Moreover, the ABCA1, ABCG1, SCARB1, hsa-miR-33a and hsa-miR-128a expression analysis revealed that hyper group presents a significant increase of ABCA1 and ABCG1 expression in relation to the control group; additionally, hsa-miR-33a decreased by 72%. Together, these results indicate a potential regulatory role of this miRNA in asymptomatic individuals, probably contributing to increased cholesterol efflux and reverse cholesterol transport
Doutorado
Ciencias Biomedicas
Doutora em Ciências Médicas

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Bamji-Mirza, Michelle. "Defining an Intracellular Role of Hepatic Lipase in the Formation of Very Low Density Lipoproteins and High Density Lipoproteins." Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/20134.

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Hepatic lipase (HL) plays a pivotal role in the catabolism of apolipoprotein (apo)B-containing lipoproteins and high density lipoprotein (HDL) particles through its reported catalytic and non-catalytic extracellular functions. The current study tested the hypothesis that HL expression might impair formation and secretion of hepatic derived very low density lipoproteins (VLDL) and apoA-I (nascent HDL). Stable or transient expression of human HL (hHL) in McA-RH7777 cells resulted in decreased incorporation of [3H]glycerol into cell-associated and secreted (VLDL-associated) 3H-triacylglcyerol (TAG) relative to control cells. Stable expression of catalytically-inactive hHL (hHLSG) also resulted in decreased secretion of VLDL-associated 3H-TAG whereas cell-associated 3H-TAG levels were unchanged. Expression of hHL or hHLSG increased cell-associated 35S-apoB100 with relatively no change in secreted 35S-apoB100. Importantly, hHL or hHLSG expression resulted in reduced 3H-TAG associated with the microsomal lumen lipid droplets (LLD), and increased relative expression of ApoB and genes involved in lipogenesis and fatty acyl oxidation. Transient expression of hHL in HL-null primary hepatocytes, mediated by adenoviral gene transfer, resulted in decreased steady-state levels of cell-associated and secreted apoA-I and reduced rates of synthesis and secretion of 35S-apoA-I. HL-null hepatocytes exhibited increased levels of secreted 35S-apoA-I relative to wildtype hepatocytes while cell-associated 35S-apoA-I levels were normal. Transient expression of a hHL chimera (hHLmt), in which the C-terminus of hHL was replaced with mouse HL sequences, exerted an inhibitory effect on apoA-I production similar to that of hHL even though hHLmt was secreted less effectively than hHL with impaired exit from the endoplasmic reticulum (ER) as compared with hHL. In contrast, stable expression of hHL in McA-RH7777 cells resulted in a dose-dependent increase in cell-associated and secreted 35S-apoA-I levels. These studies demonstrate that hHL has an intracellular (but non-catalytic) role in reducing the content of the LLD and ultimately the buoyancy of secreted VLDL particles, and that the N-terminal sequences of ER-residing hHL directly or indirectly modulates the production and secretion of apoA-I (nascent HDL) from hepatocytes.

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Sachet, Julio Cesar. "Cinética plasmática de emulsão lipídica semelhante à lipoproteína de baixa densidade (LDL) no lúpus eritematoso sistêmico com e sem difosfato de cloroquina." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5145/tde-01112006-224013/.

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Abstract:

OBJETIVO: A via metabólica da lipoproteína de baixa densidade (LDL) em pacientes com lúpus eritematoso sistêmico (LES) em uso de difosfato de cloroquina (DFC) foi avaliada através do comportamento cinético de uma nanoemulsão radioativa rica em colesterol (LDE) que se assemelha à estrutura lipídica da LDL. MÉTODOS: LDE foi marcada com 14C-colesterol éster (14C-CE), sendo a seguir injetada endovenosamente em pacientes do sexo feminino com LES inativo: 10 tomando DFC (grupo DFC), 10 sem tratamento (grupo SEM TRATAMENTO); e 10 mulheres normais (grupo CONTROLE). Os grupos foram pareados pela idade e seguiram rigorosos critérios de seleção de condições que pudessem interferir no perfil lipídico. Amostras de sangue foram coletadas em intervalos pré-estabelecidos após a infusão para mensuração da radioatividade. Níveis séricos de jejum de lipoproteínas foram determinados no início dos estudos cinéticos. RESULTADOS: Idade e índice de massa corpórea (IMC) foram similares nos grupos estudados. A taxa fracional de remoção (TFR) de 14C-CE foi significativamente maior no grupo DFC comparada ao grupo SEM TRATAMENTO (0,076 ± 0,037 vs. 0,046 ± 0,021 h-1; p < 0,05) e CONTROLE (0,0516 ± 0,0125 h-1; p < 0,05). Em concordância, níveis significativamente menores de colesterol total e LDL foram observados no grupo DFC (156 ± 16 e 88 ± 16 mg/dl) comparando-se com SEM TRATAMENTO (174 ± 15 e 108 ± 17 mg/dl; p < 0,05) e CONTROLE (200 ± 24 e 118 ± 23 mg/dl; p < 0,05). Além disso, o incremento em 50% na TFR de 14C-CE no grupo DFC foi acompanhado por uma redução em 20% no LDL-C comparando-se a SEM TRATAMENTO. CONCLUSÃO: Esta é a primeira demonstração in vivo que a remoção de LDE do plasma encontra-se aumentada em pacientes com LES em uso de DFC. Estes dados suportam o benefício desta droga no tratamento do LES e identificam o receptor de LDL como um mecanismo promissor de DFC na redução de lípides em pacientes tomando corticosteróides.
OBJECTIVE: Low-density lipoprotein (LDL) pathway in systhemic lupus erythematosus (SLE) patients taking chloroquine diphosphate (CDP) was evaluated through the kinetic behavior of a radioactive cholesterol-rich nanoemulsion (LDE) that resembles the LDL lipidic structure. METHODS: LDE was labeled with 14C-cholesteryl ester (14C-CE), then IV injected in inactive female SLE patients: 10 taking CDP (CDP), 10 without therapy (NO THERAPY); and 10 normal subjects (CONTROL). Groups were age-matched and followed rigorous selection criteria of conditions that interfere in the lipid profile. Blood samples were collected in pre-established intervals after infusion for radioactivity measurement. Fasting lipoproteins were determined in the beginning of kinetic studies. RESULTS: Age and body mass index (BMI) were similar in the studied groups. Fractional clearance rate (FCR) of 14C-CE was significantly greater in CDP compared to NO THERAPY (0.076 ± 0.037 vs. 0.046 ± 0.021 h-1; p < 0.05) and CONTROL (0.0516 ± 0.0125 h-1; p < 0.05). Accordingly, a significant lower total and LDL cholesterol were observed in CDP (156 ± 16 and 88 ± 16 mg/dl) compared to NO THERAPY (174 ± 15 and 108 ± 17 mg/dl; p<0.05) and CONTROL (200 ± 24 and 118 ± 23 mg/dl; p < 0.05). Moreover, the 50% increase in 14C-CE FCR in CDP was paralleled by 20% decrease in LDL-c compared to NO THERAPY. CONCLUSION: This is the first in vivo demonstration that removal of LDE from plasma was increased in SLE patients taking CDP. These data support its beneficial use in SLE and identify the LDL receptor as a promising CDP mechanism for lowering lipids in patients taking corticosteroids.

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Dissertations / Theses on the topic 'Lipoproteins'

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