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1
Burton, Victoria Jane. "Neutrophil migration through endothelial cells and their basement membrane." Thesis, University of Birmingham, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.532273.
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Secor, Jordan Douglas. "Phytochemical Antioxidants Induce Membrane Lipid Signaling in Vascular Endothelial Cells." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1338391553.
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Kline, Michelle A. "Membrane cholesterol regulates vascular endothelial cell viability, function, and lipid signaling." Connect to resource, 2008. http://hdl.handle.net/1811/32175.
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Alhumaid, Haidar S. "Nanoanalytical Studies of Bacterial Adhesion to the Membrane of Endothelial Cells." Ohio University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1470946411.
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Levy, Somin Gabriel. "The iridocorneal-endothelial syndrome : a study of cell and basement membrane pathology." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309311.
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Charles-Orszag, Arthur. "Cellular and molecular mechanisms of human endothelial cell plasma membrane remodeling by Neisseria meningitidis." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB045/document.
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Neisseria meningitidis est une bactérie diderme qui colonise le nasopharynx humain de façon commensale. Occasionnellement, elle franchit la barrière nasopharyngée et accède à la circulation sanguine où elle peut provoquer un choc septique et/ou une méningite Le pouvoir pathogène de N. meningitidis est lié à sa capacité à interagir avec les cellules endothéliales humaines. Après avoir adhéré aux cellules grâce à des organelles filamenteux, les pili de type IV, les bactéries induisent une déformation de la membrane plasmique de la cellule hôte sous la forme de protrusions riches en actine ressemblant à des filopodes. Ces protrusions permettent aux bactéries de résister aux forces de cisaillements générées par le flux sanguin et de proliférer à la surface des cellules. Contrairement à de nombreuses autres bactéries pathogènes, cette déformation de la membrane plasmique ne nécessite pas de polymérisation d’actine. Cependant, les mécanismes cellulaires et moléculaires de cette déformation sont inconnus. Dans cette étude, nous montrons que lorsque des bactéries individuelles adhèrent à la cellule hôte, la membrane plasmique se déforme en adhérant le long des fibres de pili de type IV de façon similaire au mouillage d’un liquide sur un solide. Les pili de type IV agissent donc comme un échafaudage extracellulaire qui guide les protrusions de membrane plasmique indépendamment du cytosquelette d’actine. Nous montrons également que la capacité de la membrane plasmique à se déformer le long de structures adhésives nanométriques est une propriété intrinsèque des cellules endothéliales. Ces travaux décrivent le mécanisme d’une étape importante de la pathophysiologie de N. meningitidis et mettent en évidence des propriétés nouvelles de la membrane plasmique des cellules humaines qui pourraient être impliquées dans d’autres processus fondamentaux de biologie cellulaireNeisseria meningitidis is a diderm bacterium that is naturally found in the human nasopharynx as a commensal. Occasionally, it can cross the mucosa and reach the underlying blood vessels where it enters the circulation. Once in the bloodstream, it can cause severe septic shock and/or meningitis. The ability of N. meningitidis to cause disease is tightly linked to its ability to interact with human endothelial cells. In particular, upon bacterial adhesion via filamentous organelles called type IV pili, bacteria remodel the host cell plasma membrane in the form of actin-rich, filopodia-like protrusions. These protrusions allow bacteria to resist blood flow-generated shear stress and proliferate on top of the host cells. Unlike many other bacterial pathogens, plasma membrane remodeling induced by N. meningitidis does not require actin polymerization. Yet, the cellular and molecular mechanisms of this process are unknown. Here, we show that upon adhesion of individual bacteria, the host cell plasma membrane deforms by adhering along type IV pili fibers in a wetting-like fashion. Therefore, type IV pili act as an extracellular scaffold that guide plasma membrane protrusions in an F-actin-independent manner. We further show that the ability of the plasma membrane to deform along nanoscale adhesive structures is an intrinsic property of endothelial cells. Therefore, this study uncovers the mechanism of a key step of N. meningitidis pathophysiology and reveals novel properties of human cell plasma membrane that could be at play in other fundamental cellular processes
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Saavedra, García Paula. "FABP4: interactions with endothelial cell plasma membrane and effects on vascular smooth muscle cells." Doctoral thesis, Universitat Rovira i Virgili, 2016. http://hdl.handle.net/10803/348560.
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Fatty acid-binding protein 4 (FABP4) és una adipoquina secretada pel teixit adipós implicada en la regulació del metabolisme energètic i la inflamació. S'han detectat nivells elevats de FABP4 circulant en persones amb factors de risc cardiovascular i aterosclerosi, encara que no hi ha moltes dades sobre FABP4 i l'aterosclerosi en humans. Alguns estudis han demostrat que FABP4 té un efecte directe sobre els teixits perifèrics, concretament promovent la disfunció endotelial. La disfunció endotelial juga un paper clau en el desenvolupament de lesions ateroscleròtiques, així com la migració i proliferació de cèl·lules de múscul llis vascular. No obstant això, el mecanisme d'acció i funcions de FABP4 circulant són poc conegudes. La hipòtesi d'aquest treball és que FABP4 interacciona amb teixits perifèrics contribuint a la disfunció endotelial i remodelació vascular a partir de la interacció amb proteïnes de membrana plasmàtica, que actuarien com a elements d'ancoratge i/o receptors mitjançant rutes de senyalització intracel·lular, i/o internalització.
Els nostres resultats indiquen que FABP4 exògena interactua específicament amb citoqueratina 1 (CK1) en les membranes cel·lulars endotelials i la seva inhibició farmacològica per BMS309403 disminueix lleugerament la formació d'aquests complexos. A més, FABP4 exògena travessa la membrana plasmàtica per entrar al citoplasma i nucli de cèl·lules endotelials (HUVECs). També hem demostrat que FABP4 exògena forma un complex amb CK1 en les cèl·lules del múscul llis vascular (HCASMCs) i que té un efecte directe induint la migració i proliferació de les HCASMCs a través de l'activació de la via de senyalització MAPK per la fosforilació de ERK1/2 i activació dels factors de transcripció nuclears c-myc i c-jun. Aquests resultats suggereixen que FABP4 circulant podria tenir un paper en el remodelat vascular i progressió de l'aterosclerosi. Aquestes dades contribueixen al nostre coneixement actual sobre el mecanisme d'acció de FABP4 circulant.Fatty acid-binding protein 4 (FABP4) es una adipoquina secretada por el tejido adiposo implicada en la regulación del metabolismo energético y la inflamación. Se han detectado niveles elevados de FABP4 circulante en personas con factores de riesgo cardiovascular y aterosclerosis, aunque no hay muchos datos sobre FABP4 y aterosclerosis en humanos. Algunos estudios han demostrado que FABP4 tiene un efecto directo sobre los tejidos periféricos, concretamente promoviendo la disfunción endotelial. La disfunción endotelial juega un papel crucial en el desarrollo de lesiones ateroscleróticas, así como la migración y proliferación de células de músculo liso vascular. Sin embargo, el mecanismo de acción y las funciones de FABP4 circulante son desconocidos. La hipótesis de este trabajo es que FABP4 interacciona con tejidos periféricos contribuyendo a la disfunción endotelial y remodelación vascular a partir de la interacción con proteínas de membrana plasmática, que actuarían como elementos de anclaje y/o receptores mediando rutas de señalización intracelular, y/o internalización. Nuestros resultados indican que FABP4 exógena interactúa específicamente con citoqueratina 1 (CK1) en las membranas celulares endoteliales y su inhibición farmacológica por BMS309403 disminuye ligeramente la formación de estos complejos. Además, FABP4 exógena atraviesa la membrana plasmática para entrar en el citoplasma y núcleo de células endoteliales (HUVECs). También hemos demostrado que FABP4 exógena también forma un complejo con CK1 en las células del músculo liso vascular (HCASMCs) y que tiene un efecto directo sobre la migración y proliferación de HCASMCs a través de la activación de la vía de señalización MAPK por la fosforilación de ERK1/2 y activación los factores de transcripción nucleares c-myc y c-jun. Estos resultados sugieren que FABP4 circulante podría tener un papel en el remodelado vascular y en la progresión de la aterosclerosis. Estos datos contribuyen a nuestro conocimiento actual sobre el mecanismo de acción de FABP4 circulante.
Fatty acid-binding protein 4 (FABP4) is an adipose tissue-secreted adipokine that is involved in the regulation of energetic metabolism and inflammation. Increased levels of circulating FABP4 have been detected in individuals with cardiovascular risk factors and atherosclerosis, although there is not much data on FABP4 in human atherosclerosis. Some studies have demonstrated that FABP4 has a direct effect on peripheral tissues, specifically promoting endothelial dysfunction. Endothelial dysfunction plays crucial roles in the development of atherosclerotic lesions as well as migration and proliferation of vascular smooth muscle cells. However, the mechanism of action and functions of circulating FABP4 are unknown. The hypothesis of this study is that circulating FABP4 has a direct effect on peripheral tissues. In particular at vessel wall level, FABP4 contributes to endothelial dysfunction and artery wall remodelling through interaction with endothelial plasma membrane proteins that act as anchoring elements and/or receptors mediating intracellular signalling, and/or FABP4 internalization. FABP4 acts on smooth muscle cells influencing cell migration and proliferation as well. Our results indicate that exogenous FABP4 interacts with specifically CK1 on endothelial cell membranes and the pharmacological FABP4 inhibition by BMS309403 decreases the formation of these complexes slightly. Furthermore, exogenous FABP4 crosses the plasma membrane to enter the cytoplasm and nucleus in HUVECs. In addition, we also demonstrated that exogenous FABP4 forms a complex with CK1 on vascular smooth muscle cells (HCASMCs) and has a direct effect of FABP4 on the migration and proliferation of HCASMCs through the activation of the ERK1/2 MAPK signalling pathway and activating the nuclear transcription factors c-myc and c-jun. Taking all these results together, it suggests that circulating FABP4 could have a role in vascular remodelling and atherosclerosis progression. These data contribute to our current knowledge regarding the mechanism of action of circulating FABP4.
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Brockmann, Tobias [Verfasser]. "Klinisch-experimentelle Ergebnisse nach „Descemet Membrane Endothelial Keratoplasty“ unter Verwendung von Trypanblau / Tobias Brockmann." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2019. http://d-nb.info/1191180875/34.
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Wardeh, Rima [Verfasser], and Walter [Akademischer Betreuer] Sekundo. "Long-Term Results after DMEK (Descemet’s Membrane Endothelial Keratoplasty) / Rima Wardeh ; Betreuer: Walter Sekundo." Marburg : Philipps-Universität Marburg, 2020. http://d-nb.info/1205879730/34.
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Sandberg, Christina Ann. "Vascular Endothelial Growth Factor in the Aqueous Humor of Dogs With and Without Intraocular Disease." Thesis, Virginia Tech, 2009. http://hdl.handle.net/10919/43367.
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Vascular endothelial growth factor A (VEGF) is a potent mediator of blood vessel formation throughout the body. Intraocular diseases characterized by inflammation, hypoxia or neoplasia induce new blood vessel formation within the eye. The end result of such blood vessel formation may be blinding sequellae such as glaucoma from outflow obstruction or hyphema from intraocular hemorrhage. Elevated VEGF concentrations in the aqueous humor and vitreous are documented in a number of human intraocular disease processes, including tumors, retinal detachment and uveitic glaucoma. Pharmacotherapy inhibiting VEGF expression demonstrates promise for control of some of these ophthalmic conditions. We quantified and compared VEGF concentrations in canine aqueous humor samples from 13 dogs with normal eyes and 226 eyes from 178 dogs with a variety of ophthalmic diseases by ELISA. Dogs with primary cataract, diabetic cataract, primary glaucoma, uveitic glaucoma, aphakic/pseudophakic glaucoma, retinal detachment, lens luxation and neoplasia were evaluated. Elevated VEGF concentrations were found in all disease conditions tested as compared to normal dogs excepting cataracts and diabetic cataracts. Elevated aqueous humor VEGF concentrations were found in dogs with pre-iridal fibrovascular membranes (PIFM) as compared to dogs without PIFM. These results are consistent with the hypothesis that VEGF has a role in the causation or progression of a variety of canine ocular disorders.Master of Science
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Almeda, Dariela. "Investigating the effect of liposomal membrane fluidity and antibody lateral mobility on endothelial cell targeting." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11622.
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Atherosclerosis is initiated by the adhesion of leukocytes to the endothelial surface of arteries followed by migration beneath the intima. Current therapies to combat atherosclerotic plaque, such as statins or antihypertensive drugs, treat atherosclerosis indirectly; they do not specifically target inflamed vasculature or improve the vascular condition. Few studies have focused on antibody mobility or membrane fluidity as an approach to improve drug delivery vehicle binding and uptake.Engineering and Applied Sciences
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Morss, Alisa Sharon. "Endothelial cells and basement membrane : a co-regulatory unit for fibroblast growth factor-2 in hyperglycemic stress." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/36167.
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Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2006.Includes bibliographical references.
Endothelial cells and basement membrane interact as a biochemical and mechanical co-regulatory unit. The wide spectrum of manifestations of diabetic vascular disease could be related to altered kinetics of vasoactive compounds within this regulatory unit. We hypothesized that hyperglycemic stress mediates storage, release, and function of fibroblast growth factor-2 (FGF-2) through changes in interaction between endothelial cells and basement membrane. We discovered that basement membrane associated FGF-2 increased linearly with culture glucose concentration. Using novel assays, we demonstrated that FGF-2 binding kinetics were surprisingly unchanged over a range of basement membrane culture glucose. Instead, the combination of increased endothelial cell apoptosis-associated FGF-2 release and enhanced endothelial cell permeability allowed more FGF-2 to bind into the basement membrane. Such high levels of basement membrane FGF-2 abrogated the effects of hyperglycemia on proliferation but not apoptosis. An FGF-2 stimulus returned endothelial cell proliferation close to euglycemic levels, but increased apoptosis was still evident as FGF-2 signaling down an intracellular survival pathway was inhibited by glucose.
(cont.) These same findings were confirmed in vivo where FGF-2 levels were elevated in the aortic subendothelial space of diabetic animals. This thesis suggests a new paradigm for active cellular control of basement membrane and indicates the complexities of growth factor signaling in endothelial cells. Characterization of the interaction between endothelial cells and basement membrane in health and disease may advance our understanding of diabetic vascular disease and lead to development of novel biomimetic materials for therapeutic intervention.
by Alisa Sharon Morss.
Ph.D.
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Baggott, Rhiannon Rebecca. "Role of the plasma membrane calcium ATPase as a negative regulator of angiogenesis." Thesis, University of Wolverhampton, 2014. http://hdl.handle.net/2436/332139.
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Angiogenesis is the formation of new blood vessels from pre-existing ones. Unregulated angiogenesis is associated with several diseases such as diabetic retinopathy and tumour growth. Many signal transduction pathways have been implicated in the regulation of angiogenesis such as p38 mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 kinase (PI3K), extracellular signal-related kinase 1/2 (Erk1/2) and of particular interest the calcineurin/nuclear factor of activated T-cell (NFAT) pathway. Inhibition of calcineurin activity by the drug cyclopsorin A (CsA) has been shown to inhibit processes required for successful angiogenesis such as in vitro cell migration, tube formation and additionally attenuates corneal angiogenesis in vivo. CsA is associated with severe side effects and therefore the identification of an endogenous regulator of this pathway would be beneficial. One possibility is the plasma membrane calcium ATPases (PMCAs). These high affinity calcium extrusion pumps have been shown to interact with calcineurin in mammalian cells and cardiomyocytes and down-regulate the calcineurin/NFAT pathway. This is hypothesised to be due to the interaction between the two proteins which maintains calcineurin in a low calcium micro-environment generated by the calcium removal function of the pump. Interestingly, PMCA4 has been shown to interact with calcineurin in endothelial cells. The aim of our study was to further our understanding of PMCA4s regulation of the calcineurin/NFAT pathway specifically in endothelial cells and establish if PMCA4 has a role in the regulation of angiogenesis. ‘Gain of function’ by adenoviral over-expression of PMCA4 and ‘loss of function’ by either si-RNA mediated knockdown of PMCA4 or isolation of PMCA4-/- MLEC were used as models. Over-expression of PMCA4 in HUVEC resulted in inhibition of the calcineurin/NFAT pathway with the opposite result occurring in the case of the knockout of PMCA4, identifying PMCA4 as a negative-regulator of the calcineurin/NFAT pathway in endothelial cells. Over-expression of PMCA4 significantly attenuated VEGF-induced protein and mRNA expression of the pro-angiogenic proteins RCAN1.4 and Cox-2, endothelial cell migration and in vitro and in vivo tube formation with the opposite result occurring in knockdown or knockout studies, confirming PMCA4 as a down-regulator of angiogenesis. Interestingly, over-expression or knockdown of PMCA4 had no effect on VEGF-induced HUVEC proliferation or Erk1/2 phopshorylation proposing PMCA4 may be a potential inhibitor of angiogenesis without compromising cell survival. Disruption of the interaction between PMCA4 and calcineurin by generation and ectopic expression of an adenovirus encoding the region of PMCA4 that interacts with calcineurin (428-651) (Ad-ID4) resulted in an increase in NFAT activity, RCAN1.4 protein expression and in vitro tube formation. These results identify the mechanism of PMCA4s inhibitory effect of the calcineurin/NFAT pathway and consequently angiogenesis is a result of the interaction between the two proteins. The novel findings of this study establish PMCA4 as a negative-regulator of the calcineurin/NFAT pathway in endothelial cells and angiogenesis. These results are far reaching and highlight a potential role for PMCA4 as a therapeutic target in a variety of diseases that are associated with pathological angiogenesis.
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Giedt, Randy James. "Real-Time Acquisition and Analysis of Endothelial Mitochondrial Superoxide Radical Production and Membrane Potential During In Vitro Ischemia/Reperfusion." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1243541457.
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Syme, C. A. "Patch-clamp studies on endothelial cell and chromaffin cell K'+ channels : effects of shear stress, membrane stretch and fatty acids." Thesis, University of Strathclyde, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298575.
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Hillman, David James. "Membrane currents evoked by vasoactive compounds in vascular endothelial cells : contributions of small and intermediate conductance calcium-activated potassium channels." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445578/.
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The contribution of different calcium-activated potassium channel subtypes to agonist-evoked whole-cell currents was studied in cultured pig coronary artery endothelial cells. From a resting membrane potential of-5.9 0.5mV (n=102), 1-lOuM ATP, 1-1 OnM substance P and 1-lOOnM bradykinin hyperpolarised cell rafts to -50.7 1.6mV (n=76), -45.7 4.7mV (n=19) and -59.1 3.5mV (n=16), respectively. In small clusters of cells, 1 OuM ATP evoked outward currents which reversed close to EK and were sensitive to both the SKca channel blocker UCL 1848 (IC5o 1.2nM -65% maximal block) and the IKca/BKca channel blocker charybdotoxin (-85% block at 30-100nM). Surprisingly lOuM clotrimazole, a non selective blocker of IKca channels, abolished ATP-evoked currents in a total of three out of five cells. This requires further study. ImM 1-EBIO, which increases the calcium sensitivity of SKca and IKca channels, activated currents which were sensitive to lOOnM UCL 1848 and luM clotrimazole (blocked by 57.0 15.1% (n=3) and 89.0 1.6% (n=4), respectively). When applied in combination, these two blockers essentially abolished 1-EBIO evoked currents. Buffering intracellular calcium to 1.5uM activated outward currents which were sensitive to lOOnM UCL 1848, lOOnM charybdotoxin and lu.M clotrimazole (blocked by 28.3 5.4% (n=27), 101.2 0.5% (n=3), and 82.6 3.7% (n=22), respectively. Plasma membrane delimited expression of the SK3 channel protein was detected using fluorescence immunohistochemistry. In many vessels endothelium-derived hyperpolarising factor (EDHF)- mediated vasodilation is abolished by a combination of SKca and IKca channel blockers, which are frequently ineffective when applied alone. This has led some to suggest the existence of a novel channel with unusual pharmacology. The present study demonstrates, however, that separate SKca and IKca channels contribute to endothelial cell currents underlying the EDHF pathway. Based on protein expression and UCL 1848-sensitivity it is further proposed that the contributing SKca channels are formed of SK3 subunits.
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Abdin, Alaa Din [Verfasser]. "Impact of dextran in organ culture media for preservation of DMEK (Descemet Membrane Endothelial Keratoplasty) precut tissue / Alaa Din Abdin." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2020. http://d-nb.info/1216104832/34.
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DELLA, PORTA MATTEO. "FATTY ACIDS UNSATURATION AND OXIDATIVE STRESS IN MEMBRANE FUNCTION, PREGNANCY, AND METABOLIC SYNDROME." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/824544.
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Fatty acids have biological activities that go far beyond their function as energy sources. A correct
the dietary ratio between the nutritionally essential ω‐6 and ω‐3 polyunsaturated fatty acids (PUFA)
is fundamental for the physiological production of second messengers, such as eicosanoids and
other autacoids, and to ensure a controlled biological response to numerous physiological and
pathological processes. Besides, PUFA, because of the unsaturation of their carbon chains, play
an important role in maintaining the structure and a correct fluidity state of the membranes, the
latter is a factor that directly regulates the activity of membrane-bound proteins, including
ATPase pumps. However, the higher the degree of PUFA unsaturation the higher is their
peroxidability. Lipid peroxidation (LPO) is a degrading process that, proceeding through a chain
reaction mechanism, produces various cytotoxic and pro-inflammatory substances involved in
the etiopathogenesis of numerous pathologies, including cerebro- and cardiovascular diseases
and type 2 diabetes mellitus. Several studies suggest protective effects of PUFA on cardiometabolic
risk, but in recent years some studies have also reported potential negative effects.
Based on these premises I collaborated on four studies aimed at evaluating: i) the effects of dietary
supplementation with a multivitamin and ω-3 PUFA (MVP) on maternal biomarkers during the
second and third trimester of pregnancy; (ii) the effects of ω-3 PUFA enrichment in endothelial
cell membranes on LPO and the activity of the Na, K pump, which plays an important role in
regulating the vascular tone of endothelial myocytes; (iii) the effects of diet-induced weight loss
on the lipid composition of lipoproteins, peripheral cytokine levels and metabolic endotoxemia
in obese subjects with metabolic syndrome (MetS); and vi) the chemical characterization of
plasma lipoproteins by Raman microspectroscopy (RS). The first was a multicenter, randomized,
and parallel study demonstrating that MVP supplementation led to a significant increase in
concentrations of erythrocytic docosahexaenoic acid (DHA), omega-3 index, and vitamin D
levels, while it did not affect the state of oxidative stress during pregnancy. These findings are
important considering the essential roles of DHA in the developing brain, in visual development,
and immunomodulation of the fetus. The results of the second study showed that as
concentrations of EPA and DHA increase, the degree of fluidity and susceptibility to peroxidation
increases in endothelial cell membranes. Besides, it has been observed that Na, K pump activity
peaked at a concentration of 3.75 μM of the two PUFA, and then gradually decreased. This study
highlights that low concentration EPA and DHA minimizes peroxidation potential and optimizes
pump activity. The third study revealed a caloric-restriction-induced substantial transfer of
triacylglycerols from VLDL and LDL to HDL that could impair the functionality of the latter,
along with positive effects on inflammatory markers in a small group of subjects with MetS. In
addition, an interesting positive correlation was also observed among peripheral cytokines levels
after diet and peripheral levels of cholesteryl ester transfer protein, an enzyme with a key role in
lipoprotein remodelling. Finally, the latest study allowed the determination of the chemical
composition of the main classes of lipoproteins through RS identification and characterization of
the spectra of cholesterol, triacylglycerols, apolipoproteins and carotenoids in a very small
amount of samples. This study paves the way for the application of this technique in clinical
nutritional studies and on a better understanding of several metabolic and pathological
conditions.
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Pancotto, Theresa E. "Evaluation of cerebrospinal fluid biomarkers of endothelial damage and basement membrane degradation as indirect indicators of blood-brain barrier dysfunction in chronic canine hypothyroidism." Thesis, Virginia Tech, 2011. http://hdl.handle.net/10919/76955.
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A variety of neurologic illnesses including peripheral and cranial neuropathies, central vestibular disease, seizures and coma have been associated with hypothyroidism in dogs. Repeated studies have shown that there is loss of blood brain barrier (BBB) integrity in these animals. Current research has also shown the development cerebrospinal fluid abnormalities in neurologically normal hypothyroid dogs; a finding that is related to BBB degradation. This derangement may be secondary to atherosclerosis and vascular accidents. One possible mediator of vasospasm and ischemic brain injury is endothelin-1 (ET-1). Another group of mediators of vascular dysfunction that has been found in CSF of dogs with various other CNS diseases is matrix metalloproteinases (MMP). The purpose of this study was to assay molecular markers that may contribute to disruption in the blood brain barrier in chronically hypothyroid canines. We hypothesized that BBB disruption in hypothyroidism is mediated by ET-1 and MMPs, as evidenced by increased concentrations of these proteins in CSF compared to controls.
Cerebrospinal fluid (CSF) previously collected from 9 control and 9 experimentally induced hypothyroid dogs was used. Administration of I-131 was used to create the experimental model. CSF from time points 0, 6, 12, and 18 months post-induction were evaluated using an ELISA kit for endothelin-1. CSF from each time point was also evaluated using gelatinase zymography to detect MMP-2,9, and 14.
The endothelin assay was able to detect ET-1 in CSF as determined by a spike and recovery method. However, ET-1 was undetectable in CSF of control and hypothyroid dogs at all time points. Constitutively expressed MMP-2 was detectable in all dogs at all time points. No other MMPs were detectable in CSF.
ET-1 and gelatinase MMP,-9, and -14 are not primary mediators of BBB damage in chronically hypothyroid dogs. They could be involved secondarily and may be better evaluated with different assays or in temporal association with the development of clinical signs of neurologic dysfunction. Additional research is needed to confirm this finding and to evaluate biomarkers of non-vascular components of the BBB.Master of Science
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Glatzel, Daniel Karl [Verfasser], Robert [Gutachter] Fürst, and Rolf [Gutachter] Marschalek. "Acetyl-CoA Carboxylase 1 (ACC1) regulates endothelial cell migration by shifting the membrane lipid composition / Daniel Karl Glatzel ; Gutachter: Robert Fürst, Rolf Marschalek." Frankfurt am Main : Universitätsbibliothek Johann Christian Senckenberg, 2018. http://d-nb.info/1164077309/34.
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Gerber, Fanny Luise [Verfasser], Björn [Gutachter] Bachmann, and Stefan [Gutachter] Haneder. "Korneale Densitometrie als diagnostischer Prädiktor für den postoperativen Visus nach Descemet membrane endothelial keratoplasty (DMEK) / Fanny Luise Gerber ; Gutachter: Björn Bachmann, Stefan Haneder." Köln : Deutsche Zentralbibliothek für Medizin, 2021. http://d-nb.info/1229352899/34.
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Murray, Iain Colquhoun. "The immunohistochemical localization of basement membrane components to secretory organelles is observed in the youngest endothelial cells of the rat incisor, suggesting that the synthesis of basement membrane components occurs mainly in young cells." Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=65989.
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Konstantoulas, Constantine James. "Genetic variants in an endothelial cell membrane protein (thrombomodulin) participating in the protein C pathway : clinical studies of heart disease and in vitro analysis." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1446452/.
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Thrombin is the key enzyme in the formation of a fibrin clot. Control of its activity and generation forms an important haemostatic function preventing occlusive blood clot formation. Deregulation of this control process results in increased thrombin generation and thus increased clot formation in thrombotic conditions. Thrombomodulin (Tm) is an important thrombin-regulatory gene expressed at the endothelial cell surface, and as such may have a role in modifying susceptibility to occlusive thrombotic disease. This thesis focuses on the role of gene variants, within Tm, in determining risk of coronary heart disease (CHD). Contribution to risk of CHD by variants in the Tm gene was assessed in a case-control study (H1FMECH), a large prospective study of heart disease (NPHSII) and a cross sectional study of type 2 diabetes (EDSC). Tm gene variant interaction with clinical and plasma markers of CHD was also studied. The consequences of Tm gene variants upon thrombin generation and inflammation were also addressed. Tm antigen levels and cofactor activity for protein C (PC) activation were assessed to determine whether the overall contribution to heart disease by dysfunctional variants could be estimated. In vitro functional studies were performed, to determine the molecular mechanisms of the effect of the variants showing strong effects on risk and to further our understanding of the role of Tm in the pathogenesis of CHD. The work included in this thesis demonstrates that genetic variation in the Tm gene may influence risk for CHD in an environment of metabolic syndrome. It adds to a growing body of evidence suggesting a contribution to CHD risk caused by variants or mutations in the Tm gene.
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Pedemonte, Sarrias Eduard. "Tècnica de Muraine per a DMEK: anàlisi comparativa amb la tècnica estàndard." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/405259.
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La queratoplàstia endotelial de la membrana de Descemet (DMEK) és la tècnica d'elecció actual per al tractament de l’edema corneal irreversible. Després que Melles la desenvolupés el 2006, Muraine va proposar el 2013 una tècnica alternativa per a la dissecció i implantació de l’empelt. Aquesta tècnica aportava dues novetats: la hidrodissecció amb trepanació parcial i curvatura corneal invertida del teixit donant i el plegament de l’empelt amb l'endoteli a la seva cara interna, que afavoria la protecció de l’endoteli i la tendència natural de l’empelt a desplegar-se a la cambra anterior del receptor.
L’objectiu d’aquesta tesi doctoral és comparar la tècnica de Muraine amb la tècnica estàndard analitzant-ne la densitat de cèl·lules endotelials (DCE) i agudesa visual (AV) postoperatòries, els temps quirúrgics i les complicacions intraoperatòries i postoperatòries. Es va dur a terme un estudi de cohorts prospectiu observacional multicèntric en la pràctica clínica habitual a l’Hospital Universitari MútuaTerrassa i l’Institut de Microcirurgia Ocular. El seguiment postoperatori va ser de sis mesos, amb controls com a mínim l’endemà, al cap d’una setmana i al cap d’un, tres i sis mesos de la cirurgia.
Es van incloure 27 ulls de 20 pacients al grup de la tècnica Estàndard i 42 ulls de 40 pacients al grup intervingut amb la tècnica Muraine. La DCE als sis mesos va ser de 1488 (1337-1679) cèl·lules/mm2 al grup Estàndard i de 1170 (734-1614) cèl·lules/mm2 al grup Muraine (P=0.10). L’AV mitja als sis mesos va ser de 0.89 al grup Estàndard i 0.79 al grup Muraine, en l’escala decimal (P=0.19). Al voltant del 80% van assolir una AV de 0.5 o més i el 50-70%, 0.8 o més.
Es va observar que la DCE i el percentatge de pèrdua de DCE al mes de la cirurgia eren equivalents als de la tècnica estàndard. El percentatge de pèrdua de DCE als sis mesos va ser superior amb la tècnica de Muraine, si bé la DCE va ser clínicament comparable. L’AV assolida als sis mesos va ser equivalent. La tècnica de Muraine va ser tan segura com la tècnica estàndard per a l’obtenció de l’empelt. La incidència de complicacions intraoperatòries amb l’empelt preparat amb la tècnica de Muraine en ulls amb facoemulsificació no complicada no va ser estadísticament superior. La dissecció de l’empelt amb la tècnica de Muraine va ser més lenta. El desplegament, per contra, va ser lleugerament més ràpid. Totes dues tècniques van tenir una taxa elevada de supervivència de l’empelt. La complicació postoperatòria més freqüent en ambdós grups va ser l’edema macular quístic. Els empelts dissecats amb la tècnica de Muraine van tenir una major incidència de necessitat de reinsuflació.Descemet’s membrane endothelial keratoplasty (DMEK) is the current gold standard treatment for irreversible corneal oedema. After Melles developed this technique in 2006, Muraine proposed in 2013 an alternative technique for the dissection and implantation of the graft. Its main contributions were: hidrodissecting the graft from a partially trephined, inverted donor tissue, and folding the graft over the endothelial side, which favoured the protection of endothelial cells and the graft’s natural tendency to unfold in the receptor’s anterior chamber. The purpose of this doctoral thesis is to compare Muraine’s technique to the Standard through analysis of the postoperative endothelial cell density (ECD) and visual acuity (VA), surgical time, and intraoperative and postoperative complications. An observational, multicentric, prospective, cohorts trial was carried out in Hospital Universitari MútuaTerrassa and Institut de Microcirurgia Ocular in a daily praxis basis. There were follow-up controls over the six months following the surgery, at least at day one, first week and first, third and sixth months. Twenty-seven eyes from 20 patients were included in the Standard technique group. Forty-two eyes from 40 patients were included in the Muraine’s technique group. The ECD at six months was 1488 (1337-1679) cells/mm2 for the Standard group and 1170 (734-1614) cells/mm2 for Muraine’s group. The mean VA at six months was 0.89 for the Standard group and 0.79 for Muraine’s group, in the decimal scale (P=0.19). Around 80% of the eyes reached a VA of 0.5 or higher and 50-70%, 0.8 or higher. The ECD and the percentage of ECD loss with Muraine’s technique at the first month after surgery were equivalent to the Standard technique’s. The percentage of ECD loss at six months was higher with Muraine’s technique, although the ECD was clinically comparable. The VA achieved at six months was equivalent. Muraine’s technique was as safe as the Standard technique for the graft dissection. The incidence of intraoperative complications among the eyes with uncomplicated phacoemulsification was not statistically higher with Muraine’s technique. The graft dissection with Muraine’s technique was slower. Conversely, the unfolding was slightly faster. Both techniques had a high graft survival rate. The most frequent postoperative complication in both groups was cystoid macular oedema. The grafts dissected with Muraine’s technique had a higher incidence of need for rebubbling.
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Baldavira, Camila Machado. "Estudo do efeito da beta 2-glicoproteína I no desenvolvimento da rede vascular de membrana corioalantóica de embriões de galinha." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-28072017-134103/.
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Angiogênese é a formação de novos capilares a partir de vasos pré-existentes, mediada por eventos de sinalização bioquímica que determinam proliferação, migração, diferenciação e morte celular e controlam crescimento e remodelação tecidual. A beta2-glicoproteína I (beta2GPI) é uma proteína plasmática com ação sobre a função vascular e a aterogênese. Monomêros de beta2GPI apresentam efeito anti-inflamatório e anticoagulante; a clivagem enzimática favorece sua dimerização e induz o aparecimento de efeitos opostos. Resultados anteriores mostraram que monômeros e dímeros de beta2GPI têm efeitos diferentes sobre a proliferação e a diferenciação de células endoteliais em culturas bidimensionais utilizadas como modelo de angiogênese. Os monômeros e dímeros de beta2GPI foram obtidos por purificação fracionada e caracterizada por SDS-PAGE e ELISA, como descrito. Neste trabalho, foram utilizadas culturas tridimensionais de células humanas vasculares de cordão umbilical (HUVEC) sobre Matrigel foram utilizadas para identificar efeitos de monômeros e dímeros da beta2GPI sobre a proliferação, migração e formação de estruturas de interação celular in vitro. O monômero de ?2GPI atuou como um fator de diferenciação endotelial dependente da densidade de plaqueamento, induzindo nas culturas tridimensionais de HUVECs a formação de fenótipos alongados, prolongamentos e estruturas de interação célula-célula. A fração dimérica modulou negativamente a proliferação de HUVECs. A membrana corioalantóide (CAM) de embriões de galinha foi empregada para estudar efeitos da beta2GPI sobre a angiogênese. In ovo, o dímero de beta2GPI impediu a angiogênese e induziu a morte embrionária 48h após a exposição, enquanto o monômero permitiu o desenvolvimento do embrião até o 10º dia, apesar de induzir mudanças precoces no desenvolvimento dos vasos da membrana corioalantóide. As estruturas da microvasculatura foram analisadas através de uma abordagem morfológica quantitativa, baseada na classificação de padrões binários locais (LBP). Alvos moleculares de beta2GPI relatados anteriormente foram considerados como fonte dos efeitos observados in vitro e in ovo. Os resultados obtidos suportam dados anteriores sobre a inibição da via de sinalização de anexina-2/Akt pela beta2GPI. Adicionalmente, sugere-se a via de sinalização Notch como um alvo do efeito antiangiogênico de da beta2GPIAngiogenesis is the formation of new capillaries from pre-existing vessels, mediated by biochemical signaling events that determine proliferation, migration, differentiation and cell death, and control of tissue growth and remodeling. beta2-glycoprotein I (beta2GPI) is a plasma protein active on vascular function and atherogenesis. ?2GPI monomers present anti-inflammatory and anticoagulant effects. Enzymatic cleavage favors beta2GPI dimerization and induces the appearance of opposing effects. Previous results have shown that beta2GPI monomers and dimers induce different effects upon the proliferation and differentiation of endothelial cells in two-dimensional cultures used as an angiogenesis model. beta2GPI monomers and dimers were obtained by fractioned purification and characterized by SDS-PAGE and ELISA, as described. In this work, three-dimensional Human Umbilical Vein Endothelial Cells (HUVEC) cultures on Matrigel were used to investigate the effects of beta2GPI monomers and dimers upon proliferation, migration and in vitro formation of cellular interaction structures. The beta2GPI monomer performed as a density-dependent endothelial differentiation factor, inducing the formation of elongated phenotypes, membrane extensions and cell-cell interaction structures in three-dimensional HUVEC cultures; the dimeric fraction negatively modulated the proliferation and differentiation of HUVECs. The chorioallantoic membrane (CAM) of chicken embryos was employed to study the effects of beta2GPI upon angiogenesis. In ovo, the beta2GPI dimer prevented angiogenesis and induced embryonic death after 48h exposure, while the monomer allowed embryo development up to the 10th day, despite it induced early changes in the development of chorioallantoic membrane vessels. Microvasculature structures were evaluated through a quantitative morphology approach, based on local binary pattern classification. Previously reported molecular beta2GPI targets were then considered as the source of the observed effects in vitro and in ovo. The obtained results support previous data on the inhibition of the annexin-2/Akt signaling pathway by beta2GPI. Additionally, the Notch signaling pathway is suggested as a target of the antiangiogenic effect of beta2GPI
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Andrieux, Annie. "Diversité structurale et fonctionnelle des cytoadhésines cellulaires." Grenoble 1, 1988. http://www.theses.fr/1988GRE10054.
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Andrade, Priscila Cristina. "Estudo temporal dos colágenos (I, III, IV e V) e produtos de glicação avançada na sinóvia em modelo experimental de diabetes em ratos." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-22102018-125609/.
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Introdução: Diabetes Mellitus é caracterizada por hiperglicemia crônica, e este aumento excessivo de glicose circulante pode gerar danos vasculares e microvasculares pela deposição de produtos de gliclação avançada (AGE), principalmente em estruturas com alta vascularização, como é o caso da sinóvia. Por todas estas razões, o presente estudo estabeleceu, de maneira temporal, o processo de acomentimento sinovial, através do grau de remodelamento e as proteínas envolvidas neste processo, tido como o gatilho na lesão da articulação do joelho. Foram utilizados ratos wistar (n=60), divididos em três grupos, conforme tempo de indução ( 7, 30 e 60 dias), cada grupo era composto de 10 animais diabéticos, induzido por estreptozotocina (35mg/kg de peso) e 10 animais controle, recebendo infusão do mesmo volume de solução salina, após o tempo estipulado os animais foram sacrificados e a sinóvia coletada para as análises propostas. Análise morfológica através de colorações de hematoxilina-eosina para análise do perfil celular do tecido sinovial e Picrosírius para avaliação da histoarquitetura das fibras colágenas. A quantificação das fibras colágenas foi realizada pela coloração do Picrosírius em microscópio de luz polarizada e a caracterização e distribuição de seus tipos por imunofluorescência, para quantificação total da proteina de colágeno foi realizado a medição da 4-hidroxiprolina (HPO). Os produtos de glicação avançada foram analisados e quantificados por imufluorescência. A detecção e quantificação da imunoexpressão de marcadores bioquímicos como ET-1, TGF-B e IL17 foi realizado por método estereológico de contagem de pontos em reticulo, e como método de confirmação dos achados imunohistoquimicos foi realizado análise de expressão gênica dos Colágenos I,III, e V alfa- 1, alfa-2), por Reação de Transcrição Reversa com amplificação por PCR em Tempo Real (qRT-PCR). Resultados: Foi observado modificação da estrutura sinovial de forma temporal, acometendo inicialmente os vasos subsinoviais e tecidos adjacentes a ele, isso foi observado em tanto em análise morfológica como confirmado em quantificação por Picro em luz polarizada, as modificações se mostraram significantes nos grupos de 30 e 60 dias, quando comparado ao respectivo grupo controle, houve aumento do colágeno total, através do Picrosirius, como por dosagem de HOP. Os resultados foram confirmados por imunofluorescência com o aumento progressivo do COLI e diminuição de COLIII e COLV, o RAGE e AGE também tiveram sua expressão aumentada conforme a evolução no tempo de indução dos animais. Em análise da expressão de outras proteínas foi possível observar a detecção da ET-1 e da IL-17 nos animais diabéticos em comparação ao controle, houve também expressão significativa do TGF-B quando comparado ao respectivo controle. Na análise da expressão gênica foi possível observar aumento do COLV inicialmente, principalmente da cadeia alfa 2, do COLIII e COLI, confirmando achados histomorfométricos. Conclusão: O tecido sinovial demonstra remodelamento precoce ao redor dos vasos, essa mediação envolve o COL1 e os produtos de glicação avançada. Esta alteração no tecido sinovial pode ser responsável por desencadear o acometimento articular no diabetes mellitusIntroduction: Diabetes Mellitus is characterized by chronic hyperglycemia, and this excessive increase of circulating glucose can cause vascular and microvascular damage by the deposition of advanced glycation products (AGE), especially in structures with high vascularization, as is the case of synovium. For all these reasons, the present study established, in a temporal way, the process of synovial concomitance, through the degree of remodeling and the proteins involved in this process, considered as the trigger in the lesion of the knee joint. Wistar rats (n = 60), divided into three groups, according to induction time (7, 30 and 60 days), each group consisted of 10 diabetic animals, induced by streptozotocin (35 mg / kg body weight) and 10 animals control, receiving infusion of the same volume of saline solution, after the stipulated time the animals were sacrificed and the synovium collected for the proposed analyzes. Morphological analysis using hematoxylineosin staining for analysis of the cellular profile of the synovial tissue and Picrosírius for evaluation of the histoarchitecture of the collagen fibers. The quantification of the collagen fibers was performed by the Picrosírius staining in a polarized light microscope and the characterization and distribution of its types by immunofluorescence, the measurement of 4-hydroxyproline (HPO) was performed for the total quantification of the collagen protein. Advanced glycation products were analyzed and quantified by impuluorescence. The detection and quantification of the immunoexpression of biochemical markers such as ET- 1, TGF-B and IL17 was performed by stereological method of reticule dot counting, and as a method of confirming the immunohistochemical findings, the analysis of the collagen I, III , and V alpha-1, alpha-2), by Reverse Transcription Reaction with Real-Time PCR Amplification (qRT-PCR). Results: Modification of the synovial structure was observed temporally, initially affecting subsynovial vessels and tissues adjacent to it, this was observed in both morphological analysis and confirmed in quantification by Picro in polarized light, the modifications were significant in the groups of 30 and 60 days, when compared to the respective control group, there was increase of the total collagen, through Picrosirius, as per HOP dosage. The results were confirmed by immunofluorescence with progressive increase of COLI and decrease of COLIII and COLV, RAGE and AGE also had their expression increased as the evolution in the induction time of the animals. In the analysis of the expression of other proteins it was possible to observe the detection of ET-1 and IL-17 in diabetic animals in comparison to the control, there was also significant expression of TGF-B when compared to the respective control. In the analysis of the gene expression it was possible to observe an increase of the COLV initially, mainly of the alpha 2 chain, of the COLIII and COLI, confirming histomorphometric findings. Conclusion: Synovial tissue demonstrates early remodeling around vessels, this mediation involves COL1 and advanced glycation products. This change in synovial tissue may be responsible for triggering joint involvement in diabetes mellitus
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Jakobsson, Lars. "Modulation of Angiogenesis by Laminins and Heparan Sulfate." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7666.
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Boyd, Nolan Lee. "The effect of shear stress on caveolae formation and function in endothelial cells." Diss., Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-04082004-180030/unrestricted/boyd%5Fnolan%5Fl%5F200312%5Fphd.pdf.
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Pelletier, Fabien. "Implication des microparticules en dermatologie : étude dans le psoriasis et le mélanome." Thesis, Besançon, 2013. http://www.theses.fr/2013BESA3013.
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Les microparticules (MPs) sont des vésicules dérivées de la membrane plasmique lors de la vésiculation par les cellules stimulées. Les MPs interviennent dans l'inflammation, les communications intercellulaires et la coagulation. Tout d'abord, nous avons standardisé une méthode pour caractériser et quantifier des MPs par cytométrie en flux dans le plasma.L'implication des MPE est suggérée dans le psoriasis notamment par le rôle central du TNF-a qui est un puissant inducteur de vésiculation. Nous avons comparé les valeurs de MPs chez des patients psoriasiques à celles de donneurs sains. Les MPE étaient plus élevées chez les patients notamment les MPs de petite taille. Les MPs diminuaient sous traitements anti-TNF-a.Les MPs agissent sur la progression tumorale des cancers. Les MPs tumorales ou des cellules de l'hôte peuvent modifier les propriétés invasives de la tumeur par des propriétés transférées. Les MPs peuvent aussi interagir avec les cellules du système immunitaire. Dans le mélanome, le risque de thrombose est accru. Or, la libération de MPs conduit à un état d'hypercoagulabilité. Les MPP et les MPE étaient augmentés dans chaque stade de la maladie par rapport à une population témoin. De plus, les MPs des patients atteints de mélanome possédaient des propriétés procoagulantes. L'étude des MPs en Dermatologie permet d'appréhender de nouveaux angles de la physiopathologie des maladies inflammatoires ou en carcinogenèse. Le dosage des MPs pourrait devenir un outil intéressant de monitoring des biothérapies dans le psoriasis. Dans le mélanome, des études complémentaires permettront de déterminer si les taux de MPs constituent un facteur pronostique intéressantMicroparticles (MPs) are vesicles derived from the plasma membrane during vesiculation by the stimulated cells. MPsare involved in inflammation, intercellular communications and coagulation. First, we standardised a method tocharacterise and quantify MPs in plasma by flow cytometry.The implication of endothelial microparticles (EMPs) is suggested in psoriasis, in particular by the central role of TNF-a which is a powerful inducer of vesiculation. We compared the values of MPs in psoriatic patients to the values inhealthy donors. EMPs were higher in the patients, especially MPs of small size. MPs were reduced under anti-TNF-atreatments.MPs have an action on the tumoral development of cancers. Tumoral MPs or the host's cells can modify the invasiveproperties of the tumour through transferred properties. MPs can also interact with the cells of the immune System. Inmelanoma, the risk of thrombosis is increased, but the release of MPs leads to a state of hypercoagulability. Plateletsmicroparticles (PMPs) and EMPs were increased at each stage of the disease compared to a control population. Inaddition, MPs of patients with melanoma had procoagulant properties.The study of MPs in Dermatology allows to apprehend new approaches of the physiopathology of inflammatorydiseases or in carcinogenesis. The dosage of MPs could become an interesting tool in the monitoring of biotherapies inpsoriasis. In melanoma, additional studies will show if MPs rates are an interesting prognostic factor
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Ambrosi, Pierre. "Analyse par cytometrie en flux de douze glycoproteines de la membrane de la cellule endotheliale au repos et stimulee." Aix-Marseille 2, 1990. http://www.theses.fr/1990AIX20818.
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Luque, Yosu. "Rôle de l'épithélium et de l'endothélium rénal au cours des glomérulopathies expérimentales. Etude des glomérulonéphrites inflammatoires et des glomérulopathies toxique et hypertensive." Electronic Thesis or Diss., Paris 6, 2016. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2016PA066394.pdf.
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Les maladies glomérulaires sont une des principales causes d'insuffisance rénale terminale de nos jours et constituent un problème de santé publique. Le concept classique dans les glomérulopathies accorde à l'agression systémique immune, toxique ou hypertensive le rôle principal dans la formation des lésions glomérulaires. L'hypothèse développée dans ce manuscrit est que épithélium et endothélium, deux composants principaux du parenchyme rénal sont des acteurs majeurs dans la formation des lésions glomérulaires. Trois modèles expérimentaux de glomérulopathie (inflammatoire, toxique et hypertensive) chez la souris nous ont permis d'étudier une voie de signalisation épithéliale γC/JAK/STAT classiquement décrite dans les cellules immunitaires et le système de réponse à l'hypoxie endothéliale afin d'étayer cette hypothèse. Après avoir discuté le rôle principal classiquement attribué aux lymphocytes T dans le modèle anti-membrane basale glomérulaire, un modèle animal de glomérulonéphrite inflammatoire, nous avons démontré le rôle protecteur de la chaîne γ commune (γC) glomérulaire et de sa protéine d'aval STAT5 dans le podocyte au cours du modèle anti-MBG et de la néphropathie à l'adriamycine. Enfin, nous avons étudié le rôle protecteur de EPAS1 (HIF-2α), une sous-unité régulatrice du complexe HIF, dans l'endothélium au cours des lésions glomérulaires hypertensives. Au total, ce travail met en évidence le rôle majeur de l'épithélium et l'endothélium rénal, étroitement liés, dans la formation des lésions glomérulaires. Le parenchyme rénal représente un acteur à part entière dans la physiopathologie de ces lésions comme le montrent les travaux sur les systèmes γC/STAT5 et HIFGlomerular diseases are a leading cause of kidney failure and represent a public health problem. Classically, systemic effectors such as the immune system, drug toxicity or hypertension are thought to be the main drivers of glomerular diseases. The hypothesis developed in this manuscript is that epithelium and endothelium, the two main components of the renal parenchyma, are major players in the formation of glomerular lesions. Three experimental models of glomerular disease (inflammatory, toxic and hypertensive) in mice allowed us to study epithelial γC / JAK / STAT signaling classically described in immune cells and the endothelial hypoxia inducible system in order to support this hypothesis. After discussing the main role traditionally assigned to T cells in the anti- glomerular basement membrane model, an animal model of inflammatory glomerulonephritis, we demonstrated the protective role of the glomerular interleukin common γ chain (γC) receptor and its dependent podocyte-specific STAT5 during the anti-GBM model and adriamycin nephropathy. We then showed the protective role of endothelial EPAS1 (HIF-2α), a regulatory subunit of HIF complex in focal segmental glomerulosclerosis (FSGS) induced by angiotensin II. In total, this work highlights the important role of the closely linked renal epithelium and endothelium in the formation of glomerular lesions using three experimental models of glomerular diseases. The renal parenchyma is a full player in the pathophysiology of these lesions as shown by the works studying γC / JAK / STAT and HIF systems
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松尾, 清一, 信夫 坂本, 征郎 丸山, 由起夫 湯沢, 大裕 水谷, Seiichi Matsuo, Nobuo Sakamoto, Ikuro Maruyama, Yukio Yuzawa, and Motohiro Mizutani. "Glomerular localization of thrombomodulin in human glomerulonephritis." Thesis, the United States and Canadian Academy of Pathology, 1993. http://hdl.handle.net/2237/16374.
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Zhang, Yan. "Studies on the calcium-regulated bicarbonate ion permeability in the apical membrane of bovine corneal endothelium." [Bloomington, Ind.] : Indiana University, 2004. http://wwwlib.umi.com/dissertations/fullcit/3162273.
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Thesis (Ph.D.)--Indiana University, School of Optometry, 2004.Title from PDF t.p. (viewed Dec. 2, 2008). Source: Dissertation Abstracts International, Volume: 66-01, Section: B, page: 0050. Chair: Joseph A. Bonanno.
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Waldron, Gareth James. "A study of the influence of endothelium-derived changes in smooth muscle membrane potential on vascular tone." Thesis, University of Bristol, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241563.
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Scheitlin, Christopher Gordon. "Experimental and Computational Study of Calcium Homeostasis in Sheared Endothelial Cells: Role of Mitochondria." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1461023176.
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Piuhola, J. (Jarkko). "Regulation of cardiac responses to increased load:role of endothelin-1, angiotensin II and collagen XV." Doctoral thesis, University of Oulu, 2002. http://urn.fi/urn:isbn:9514267214.
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Abstract
Chronic overload of the heart is the major cause of left ventricular hypertrophy (LVH) and eventually heart failure. It is generally accepted that autocrine/paracrine factors, such as angiotensin II (Ang II) and endothelin-1 (ET-1) contribute to the development of LVH. Cardiac hypertrophy and failure are characterized by attenuated responsiveness to β- adrenergic stimulation and accumulation of collagenous material to the left ventricular wall. The present study aimed to characterize the roles of ET-1 and Ang II in the regulation of cardiac function. The role of the plasmamembrane Ca2+-ATPase (PMCA) in ET-1 induced cardiac responses and the role of type XV collagen in cardiac function were also studied.
Both ET-1 infusion and mechanical loading were able to induce positive inotropic effect and induction of early response genes in isolated perfused hearts. ET-1 also induced strong vasoconstriction. Cardiomyocyte-specific PMCA overexpression inhibited the ET-1 induced hypertrophic response, while inotropic response remained unaltered. ET-1 was found to induce release of adrenomedullin (AM), a potent vasorelaxing and inotropic peptide. Infusion of AM antagonized the vasoconstrictive effect of ET-1 independently of nitric oxide. In hypertrophied rat hearts ET-1 was found to contribute significantly to the Frank-Starling response, a fundamental mechanism regulating contractile performance of the heart. In mice hearts, ET-1 was found to play a dual role in load induced elevation of contractile strength: ETA receptors mediated an increase, while ETB receptors mediated an inhibitory effect on contrcatile force. Ang II was not contributing to the contractile response to load in either rat or mice hearts. Blunted response to β-adrenergic stimulus and increased vulnerability as a result of exercise was observed in mice lacking collagen XV.
In conclusion, the present results underscore the importance of the local factors, especially ET-1, in regulation of cardiac function, not only in terms of hypertrophic but also in terms of contractile response to load. The results also suggest a role for PMCA in regulation of cardiac function. Lack of type XV collagen was found to result in cardiac dysfunction with many features similar to those of early heart failure.
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Vlaeminck-Guillem, Virginie. "Specificites du gene erg, membre de la famille ets." Lille 2, 2000. http://www.theses.fr/2000LIL2T006.
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Lejoly-Boisseau, Hélène. "Etude des rapports de l'œuf de Schistosoma Mansoni avec l'endothélium vasculaire : aspects ultrastructuraux, rôle des antigènes ovulaires et des facteurs d'origine endothéliale." Bordeaux 2, 1998. http://www.theses.fr/1998BOR28577.
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Lammert, Eckhard, Vincent Laudet, Michael Schubert, Kathrin Regener, Boris Strilic, and Tomas Kucera. "Ancestral vascular lumen formation via basal cell surfaces." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-184284.
Full textAbstract:
The cardiovascular system of bilaterians developed from a common ancestor. However, no endothelial cells exist in invertebrates demonstrating that primitive cardiovascular tubes do not require this vertebrate-specific cell type in order to form. This raises the question of how cardiovascular tubes form in invertebrates? Here we discovered that in the invertebrate cephalochordate amphioxus, the basement membranes of endoderm and mesoderm line the lumen of the major vessels, namely aorta and heart. During amphioxus development a laminin-containing extracellular matrix (ECM) was found to fill the space between the basal cell surfaces of endoderm and mesoderm along their anterior-posterior (A-P) axes. Blood cells appear in this ECM-filled tubular space, coincident with the development of a vascular lumen. To get insight into the underlying cellular mechanism, we induced vessels in vitro with a cell polarity similar to the vessels of amphioxus. We show that basal cell surfaces can form a vascular lumen filled with ECM, and that phagocytotic blood cells can clear this luminal ECM to generate a patent vascular lumen. Therefore, our experiments suggest a mechanism of blood vessel formation via basal cell surfaces in amphioxus and possibly in other invertebrates that do not have any endothelial cells. In addition, a comparison between amphioxus and mouse shows that endothelial cells physically separate the basement membranes from the vascular lumen, suggesting that endothelial cells create cardiovascular tubes with a cell polarity of epithelial tubes in vertebrates and mammals.
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Pessolato, Alícia Greyce Turatti. "Caracterização das células-tronco do saco vitelino e análise ultraestrutural da membrana vitelina de embriões ovinos (Ovis aries)." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/10/10132/tde-07082012-183204/.
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O saco vitelino é o único anexo embrionário presente em todas as espécies dos embriões vertebrados, répteis, aves e mamíferos. Em mamíferos domésticos o saco vitelino é inicialmente grande, pois nestas espécies ele é transitório. Após a implantação, surge no mesênquima lateral à notocorda agrupamentos de células, denominados ilhotas sanguíneas, que representam os progenitores dos sistemas vascular e hematopoético: os hemangioblastos. Os hemangioblastos centrais das ilhas sanguíneas formam as primeiras células-tronco hematopoéticas, enquanto os hemangioblastos periféricos se diferenciam em angioblastos, os precursores dos vasos sanguíneos. O desenvolvimento inicial da atividade hematopoética no saco vitelino conduz a hipótese de que esse tecido é o local primário de desenvolvimento hematopoético e que as células-tronco derivadas dele semeiam os outros sítios intraembriônicos. Foi possível observar nas análises microscópicas que realmente existe uma relação entre ambas linhagens. Nas análises de expressão gênica, alguns genes expressos pelo hemangioblasto apresentaram alta expressão nas análises D+0 e outros genes também específicos do hemangioblasto, porém em estágios secundários de diferenciação como os encontrados na região aórtica, a nível de endotélio hemogênico apresentaram altos níveis de expressão após 3 dias em cultivo. Concluímos portanto, que o saco vitelino por ser o local primário de formação das células sanguíneas e endoteliais nos estágios iniciais da embriogênese, por serem primitivas e, portanto não expressarem marcadores de células maduras na sua superfície, tornam estas células uma importante fonte de células-tronco relevante para a Terapia Celular para hemofilia e muitas outras doenças humanas.The yolk sac is the single attachment embryo present in all species of vertebrate embryos, reptiles, birds and mammals. In domestic mammals the yolk sac is initially large, since these species it is transient. After implantation, appears in the lateral mesenchyme to the notochord cell clusters, called \"blood islands\" that represent the progenitors of vascular and hematopoietic systems: the hemangioblasts. The central islands hemangioblasts form the first blood hematopoietic stem cells, while peripheral hemangioblasts, the angioblastic differentiate into the precursors of blood vessels. The initial development of the yolk sac hematopoietic activity leads to the hypothesis that this tissue is the primary site of development and that hematopoietic stem cells derived from them sow other intraembryos sites. It was observed in the microscopic analysis that there is indeed a relationship between the two lineages. In the analysis of gene expression, some genes expressed by hemangioblasts showed high expression in D+0 and other specific genes also hemangioblasts, but in secondary stages of differentiation as found in the aortic region, the level of hemogenic endothelium showed high levels of expression after 3 days in culture. We therefore conclude that the yolk sac to be the primary site of formation of blood and endothelial cells in the early stages of embryogenesis, for its cells be primitive and therefore do not express markers of mature cells on the surface, these cells become an important source of cells relevant to stem cell therapy for hemophilia and many other human diseases.
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Caradu, Caroline. "Rôle de la voie Hedgehog dans la physiopathologie de l’ischémie critique de membre inférieur et le maintien de l’intégrité endothéliale." Thesis, Bordeaux, 2020. http://www.theses.fr/2020BORD0125.
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La prévalence du diabète et de l’ischémie critique chronique (ICC) est en constante augmentation. Ces pathologies demeurent incurables et souvent intriquées. Des résultats suggèrent que la signalisation Hedgehog (Hh) participe au maintien de l'intégrité des microvaisseaux, et une régulation négative de Desert Hh (Dhh) est associée aux facteurs de risque cardiovasculaires, tels que l'âge, le diabète et l'obésité.L’objectif principal de cette thèse était d’explorer les mécanismes physiopathologiques conduisant à l’ICC avec pour hypothèse que la protéine Dhh dérivée de l'endothélium est essentielle au maintien de l'intégrité vasculaire.Nous avons démontré que Sonic Hh (Shh) endogène ne favorise pas l'angiogenèse post-ischémie et que l'absence de Shh conduit à une inflammation tissulaire ischémique aberrante et à une angiogenèse transitoire accrue. Chez l’homme, l'ICC était associée à des capillaires dysfonctionnels plutôt qu'à une diminution de la densité capillaire et Dhh était exprimé dans les cellules endothéliales (CE). Chez la souris, une carence en Dhh induisait une activation des CE et une fuite capillaire en raison d'une altération des jonctions adhérentes. L'agoniste de la signalisation Dhh améliorait significativement la fonction des CE sans favoriser l'angiogenèse, ce qui améliorait par la suite la perfusion musculaire.Ainsi, la restauration de la fonction des CE conduit à une récupération significative de la perfusion et de la réparation musculaire dans un contexte d’ICC de membre. La voie Hh, et plus particulièrement Dhh, semble être une cible thérapeutique prometteuse pour prévenir le dysfonctionnement endothélial impliqué dans les pathologies vasculaires ischémiquesThe prevalence of diabetes and critical limb ischemia (CLI) is steadily increasing. These pathologies remain incurable and often intertwined. Results suggest that Hedgehog (Hh) signaling is involved in maintaining microvessel integrity, and downregulation of Desert Hh (Dhh) is associated with cardiovascular risk factors, such as age, diabetes, and obesity.The main objective of this thesis was to explore the pathophysiological mechanisms leading to CLI with the hypothesis that endothelial Dhh is essential for the maintenance of vascular integrity.We have shown that endogenous Sonic Hh (Shh) does not promote post-ischemic angiogenesis and that the absence of Shh leads to aberrant ischemic tissue inflammation and increased transient angiogenesis. In humans, CLI was associated with dysfunctional capillaries rather than a decrease in capillary density, and Dhh was expressed in endothelial cells (EC). In mice, Dhh knockdown was associated with EC activation and capillary leakage secondary to the alteration of adherent junctions. Dhh's agonist significantly improved EC function without promoting angiogenesis, which subsequently improved muscle perfusion.Thus, restoration of EC function leads to a significant recovery of perfusion and muscle repair in the context of CLI. The Hh signaling pathway, and more particularly Dhh, appears to be a promising therapeutic target for preventing the endothelial dysfunction involved in ischemic vascular pathologies
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Lammert, Eckhard, Vincent Laudet, Michael Schubert, Kathrin Regener, Boris Strilic, and Tomas Kucera. "Ancestral vascular lumen formation via basal cell surfaces." PLOS one, 2009. https://tud.qucosa.de/id/qucosa%3A28997.
Full textAbstract:
The cardiovascular system of bilaterians developed from a common ancestor. However, no endothelial cells exist in invertebrates demonstrating that primitive cardiovascular tubes do not require this vertebrate-specific cell type in order to form. This raises the question of how cardiovascular tubes form in invertebrates? Here we discovered that in the invertebrate cephalochordate amphioxus, the basement membranes of endoderm and mesoderm line the lumen of the major vessels, namely aorta and heart. During amphioxus development a laminin-containing extracellular matrix (ECM) was found to fill the space between the basal cell surfaces of endoderm and mesoderm along their anterior-posterior (A-P) axes. Blood cells appear in this ECM-filled tubular space, coincident with the development of a vascular lumen. To get insight into the underlying cellular mechanism, we induced vessels in vitro with a cell polarity similar to the vessels of amphioxus. We show that basal cell surfaces can form a vascular lumen filled with ECM, and that phagocytotic blood cells can clear this luminal ECM to generate a patent vascular lumen. Therefore, our experiments suggest a mechanism of blood vessel formation via basal cell surfaces in amphioxus and possibly in other invertebrates that do not have any endothelial cells. In addition, a comparison between amphioxus and mouse shows that endothelial cells physically separate the basement membranes from the vascular lumen, suggesting that endothelial cells create cardiovascular tubes with a cell polarity of epithelial tubes in vertebrates and mammals.
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Marshall, Jocelyn R. "A Study of the Impact of Membrane Organization of Glycosphingolipid E-selectin Ligands and Glycoproteins on Head and Neck Cancer Cell Adhesion to Vascular Endothelium." Ohio University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1313073422.
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Legrand, Alain. "Liposomes cibles et vecteurs retroviraux pour le transfert et l'expression du gene de la preproinsuline i de rat dans des cellules eucaryotes." Orléans, 1987. http://www.theses.fr/1987ORLE2011.
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Encapsulation d'adn dans des liposomes contenant du lactosylceramide dont le sucre terminal est reconnu specifiquement par des recepteurs presents sur la membrane plasmique des cellules visees, c. A. D. , les hepatocytes et les cellules endotheliales du foie et egalement les lymphocytes de la rate. Injection par voie intraveineuse des liposomes. Role de l'endocytose, dans leur internalisation. Modele genetique constitue du gene de la preproinsuline i de rat insere dans des vecteurs retroviraux permettant l'expression du gene dans des celules non insulogenes
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Zaric, Violeta. "Transfection endovasculaire du gène du Vascular Endothelial Growth Factor (VEGF) vectorisé par le polyéthylènimine (PEI) dans un modèle d'ischémie périphérique chez le lapin : Optimisation des formulations PEI / ADN dans une stratégie thérapeutique angiogénique." Université Louis Pasteur (Strasbourg) (1971-2008), 2003. http://www.theses.fr/2003STR13156.
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Le développement d'une circulation collatérale par des néovaisseaux bourgeonnant à partir de capillaires préexistants : angiogenèse, se développe dans les situations d'ischémie mais peut rester insuffisant face à la demande en oxygène et nutriements. Dans l'angiogenèse thérapeutique on administre un facteur angiogénique pour stimuler la vascularisation des tissus ischémiques. Le but de cette étude était de valider in vitro et dans un modèle animal d'ischémie périphérique, une thérapeutique angiogénique par transfection du gène codant pour le vascular endothelial growth factor 165 humain (VEGF165h) vectorisé par le polyéthylènimine (PEI), un polymère cationique. L'efficacité de transfection des dérivés, PEI linéaire (L-PEI) et PEI glycosylé (L-PEI-Glc4) a été comparée dans les HUVEC. Après 4 h d'incubation des complexes L-PEI-Glc4/ADN préparés dans le NaCl, le pourcentage de transfection à 24h atteint 50%, sans toxicité cellulaire majeure. En microscopie confocale, les complexes PEI/ADN s'internalisent par endocytose 2h après le début de la transfection. Ils migrent vers l'aire périnucléaire dans les 4h Lors de la transfection intra-artérielle utilisant un cathéter à ballonnet poreux chez le lapin, la formulation optimale de L-PEI-Glc4/ADN (1 mg/ml), est mise en contact 20 min avec la paroi vasculaire. Environ 10% des cellules endothéliales sont transfectées. Il n'y a pas de diffusion systémique du transgène dans les principaux organes. Chez le lapin après induction d'une ischémie périphérique, les complexes L-PEI-Glc4/VEGF sont transfectés au site de l'occlusion au septième jour. Ex vivo, la sécrétion de VEGF est 5 fois plus importante dans l'artère traitée que dans le contrôle. Trois semaines après la tansfection, le débit artériel, mesuré dans le membre ischemié est significativement plus élevé dans le groupe VEGF165 par rapport au groupe contrôle. L'angiogenèse thérapeutique par transfection génique du VEGF vectorisé par le PEI chez l'animal est efficace et sûre. Transfection endovasculaire du gène du Vascular Endothelial Growth Factor (VEGF) vectorisé par le polyéthylènimine (PEI) dans un modèle d'ischémie périphérique chez le lapin. Optimisation des formulations PEI/ADN dans une stratégie thérapeutique angiogéniqueThe spontaneous development of new collateral vessels by sprouting of preexisting capillaries: angiogenesis, occurred in ischemic tissues but may be inefficient to allow oxygen and nutriments supplies to tissues suffering ischemia. In therapeutic angiogenesis, angiogenic factors are delivered to tissues in order to stimulate the arterial growth in response to hypoxia. The aim of this work was to evaluate, in vitro and in a model of peripheral ischemia, the efficacy of an angiogenic therapeutic strategy using the gene transfer of the human vascular endothelial growth factor (VEGF165h) vectorised by, polyethylenimine (PEI), a cationic polymerThe transfection efficacies of two PEI derivatives: a linear PEI (L-PEI) and a glycosylated derivative (L-PEI-Glc4) were compared into HUVEC. After 4h of incubation, L-PEI-Glc4/DNA complexed in NaCl induced up to 50% of transfection quantified 24h later, without a major toxicity. Using confocal microscopy, the complexes internalised by endocytosis 2h after the onset of transfection. They were trafficking to the nuclear area 4h later. In rabbit, following arterial transfection with a channel catheter, the optimal L-PEI-Glc4/DNA (1 mg/ml) was infused for 20 min. Ten percent of the endothelial cells was transfected, without any systemic dissemination of the transgene in main organs. In the rabbit ischemic hindlimb model, L-PEI-Glc4/VEGF complexes were transfected at the occlusion site at day 7. Ex vivo secretion of VEGF was 5 times higher in the treated arteries compared to the control. The arterial flow measured 3 weeks after transfection at the occlusion site was significantly higher in the VEGF treated arteries than in control. Therapeutic angiogenesis by gene transfer using VEGF vectorised by PEI is efficient and safe in an animal model of peripheral ischemia
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Ampazas, Paraskevas [Verfasser], and Walter [Akademischer Betreuer] Sekundo. "Transplantatanlagerate bei Verwendung von 5% SF6- Gas versus Luft bei der Endotamponade im Rahmen der Descemet-Membran Endothelialen Keratoplastik (DMEK): Eine retrospektive Erhebung. / Paraskevas Ampazas ; Betreuer: Walter Sekundo." Marburg : Philipps-Universität Marburg, 2018. http://d-nb.info/1161847049/34.
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Cornet, Sylvie. "Evolution de la lame basale glomerulaire au cours de la nephrogenese et de la senescence, chez le rat." Paris 6, 1988. http://www.theses.fr/1988PA066166.
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Guérin, Coralie. "Biomarqueurs cellulaires circulants de la dysfonction endothéliale : détection et potentiel vasculaire." Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05P608.
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Dans la dysfonction endothéliale, le compartiment endothélial circulant joue simultanément le rôle d’acteur impliqué dans la régénération du tissu lésé et celui d’indicateur de l’état d’altération ou de régénération de l’endothélium. Dans l’artérite oblitérante des membres inférieurs (AOMI), l’un des axes de recherche porte sur le développement d’un produit de thérapie cellulaire capable d’induire la formation de néo-Vaisseaux. Face à la difficulté d’obtenir et d`amplifier des cellules progénitrices endothéliales (CPE) chez l’adulte sain, et a fortiori chez le patient, l’une des hypothèses laisse envisager le recours à d’autres types cellulaires ayant des propriétés vasculogéniques. Chez patients atteints de maladies cardiovasculaires, et d’AOMI en particulier, les cellules mononuclées de moelle osseuse et les CPE montrent des propriétés angiogéniques diminuées. Nous avons mis en évidence la capacité des cellules souches mésenchymateuses (CSM) isolées de patients atteints d’AOMI à induire une reperfusion, par recrutement de cellules endothéliales in situ, avec la même efficacité que celles de donneurs sains. Les CSM ne se différencient pas en cellules endothéliales mais agissent par paracrinie. La seconde hypothèse d’obtention d’un produit de thérapie cellulaire autologue angiogène est de trier des cellules plus immatures que les CPE afin de les différencier secondairement vers la lignée endothéliale à l’image du modèle pathologique de la cellule souche d’hémangiome CD133+ qui laisse envisager les Very Small Embryonic Like stem cells (VSEL), cellules souches multipotentes CD133+, comme un candidat de cellules post-Natales à potentiel vasculaire. Nous avons dérivés, en culture en conditions angiogéniques, des VSEL qui acquièrent un phénotype mésenchymateux mais présentent un profil sécrétoire proche de celui des CPE. Les VSEL favorisent la revascularisation post-Ischémique et acquièrent un phénotype endothélial in vitro et in vivo suggérant que les VSEL peuvent être à l’origine de la lignée endothéliale. Les VSEL se présentent également comme un biomarqueur de la dysfonction endothéliale mobilisé de la moelle osseuse (MO) vers le sang périphérique (PB) chez les patients souffrant d’AOMI. Les biomarqueurs cellulaires circulants représentent non seulement des marqueurs non invasifs de l’endothélium mais peuvent également apporter des informations utiles pour le diagnostic, le pronostic et le suivi thérapeutique des patients souffrant de pathologies associées à une dysfonction endothéliale. Une modification du nombre de CPE et de cellules endothéliales circulantes (CEC) dans la circulation a été rapportée dans différentes situations pathologiques respectivement associées à une régénération et une altération endothéliale telle l’augmentation du taux de CEC chez des patients présentant une hypertension artérielle pulmonaire (HTAP). La technique de référence pour le dénombrement des CEC dans le sang périphérique est l’immunoséparation magnétique (IMS). Cette méthode non automatisée et chronophage, repose sur l’énumération par microscopie à fluorescence des cellules CD146+ préalablement isolées. Bien que reproductible, cette numération est soumise à de nombreux biais de quantification, difficile à mettre en oeuvre et sujette à interprétation. La mise au point d’une méthode de détection automatisée des CEC par cytométrie à focalisation acoustique (AFC) s’est montrée fiable et robuste, dans une cohorte de patients atteints d’HTAP traitée ou non, constituant une alternative pertinente à l’analyse par microscopie. L’ensemble de ces travaux ouvre donc de nouvelles perspectives dans la détection des biomarqueurs cellulaires circulants impliqués dans la dysfonction endothéliale, proposant les VSEL comme nouvel acteur vasculogéniqueIn endothelial dysfunction, circulating endothelial compartment simultaneously plays the role of actor involved in the regeneration of injured tissue and reflects endothelium state. In peripheral arterial disease (PAD), one of the research areas is the development of a cellular therapy product capable of inducing the formation of neo-Vessels. Faced with the difficulty to obtain and amplify endothelial progenitor cells (EPC) in adults, one of the assumptions lets consider the use of other cell types with vasculogenic properties. In patients with cardiovascular disease, and PAD in particular, bone marrow mononuclear cells and EPC show reduced angiogenic properties. We have demonstrated the ability of isolated mesenchymal stem cells (MSCs) from PAD patients to induce reperfusion by recruitment of endothelial cells in situ, with the same efficiency as that of healthy donors MSCs. MSCs do not differentiate into endothelial cells but act by paracrine. The second hypothesis of obtaining an autologous angiogenic cell therapy product is to sort cells more immature than the CPE and to differentiate them secondarily into endothelial lineage as the pathological cell model of hemangioma stem cells CD133 + which lets consider the Very Small Embryonic like stem cells (VSEL), CD133 + multipotent stem cells as a potential candidate of postnatal vascular cell. We have derived and cultured in angiogenic conditions VSEL that acquired a mesenchymal phenotype but exhibited a secretory profile similar to that of EPC. VSEL promote post-Ischemic revascularization and acquire an endothelial phenotype in vitro and in vivo suggesting that VSEL may be responsible for the endothelial lineage. VSEL also appear as a biomarker of endothelial dysfunction mobilized from bone marrow (BM) to peripheral blood (PB) in patients with PAD. Cellular circulating biomarkers are not only non-Invasive markers of endothelium but can also provide useful information for the diagnosis, prognosis and therapeutic monitoring of patients with endothelial dysfunction associated pathologies. Changing the number of EPC and circulating endothelial cells (CEC) in the circulation has been reported in different pathological situations respectively associated with endothelial regeneration and alteration such as the increase of CEC in patients with pulmonary arterial hypertension (PAH). The reference technique for the enumeration of CEC in peripheral blood is magnetic immunoseparation (IMS). This non-Automated and time-Consuming method, based on the enumeration by fluorescence microscopy of CD146 + cells isolated. Although reproducible, this count is subject to many through quantification, difficult to implement and subject to interpretation. The development of an acoustic focusing cytometry (AFC) method for automated detection of CEC has proved reliable and robust results, in a cohort of patients with PAH treated or not, constituting a relevant alternative analysis to microscopy. All of this work opens new perspectives in the detection of cellular circulating biomarkers involved in endothelial dysfunction, suggesting VSEL as new vasculogenic actor
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Barbosa, Ana Luísa Touceira. "Endothelial Cell Loss Curve in Descemet Stripping Automated Endothelial Keratoplasty versus Descemet Membrane Endothelial Keratoplasty." Master's thesis, 2021. https://hdl.handle.net/10216/139739.
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Objetivo: Comparar a perda de células endoteliais em doentes adultos submetidos a DSAEK (Descemet stripping automated endothelial keratoplasty) ou DMEK (Descemet membrane endothelial keratoplasty) por disfunção endotelial.
Métodos: Estudo retrospetivo que incluiu 51 olhos de 51 doentes submetidos a DSAEK (23 doentes) ou DMEK (28 doentes) no Centro Hospitalar Universitário S. João (Porto, Portugal), entre abril 2015 e março 2020. Foram excluídos os doentes sem pelo menos uma determinação da densidade endotelial após o transplante e os que sofreram falência de enxerto primária. Foram analisadas as características demográficas dos doentes, a sua melhor acuidade visual corrigida (MAVC), em escala logMAR, antes e um ano após o transplante, a indicação cirúrgica, as complicações pós-operatórias e a densidade endotelial (em células/mm2), determinada através de microscopia especular, do enxerto dador antes do transplante e durante o seguimento após o mesmo.
Resultados: As características demográficas dos doentes, a indicação cirúrgica e a MAVC antes do transplante foram semelhantes nos dois grupos. A MAVC um ano após o transplante foi melhor no DMEK (0.26 ± 0.19 vs. 0.47 ± 0.29 no DSAEK; p=0.003). A densidade endotelial do enxerto dador antes do transplante foi semelhante nos dois grupos (p=0.986). A densidade endotelial após o transplante foi superior no DMEK até aos 5 meses (p<0.001), dos 5 aos 9 meses (p=0.037) e dos 9 aos 15 meses de seguimento (p=0.003), tendo sido semelhante ao DSAEK nas determinações posteriores. A perda de células endoteliais foi inferior no DMEK até 5 meses (p<0.001), dos 5 aos 9 meses (p=0.004) e dos 9 aos 15 meses de seguimento (p=0.016), tendo também sido semelhante ao DSAEK nas determinações posteriores. Dois casos de DMEK necessitaram re-injeção de ar. Dois casos de DSAEK sofreram rejeição de enxerto.
Conclusão: Na nossa coorte, o DMEK apresentou melhores resultados visuais que o DSAEK. O DMEK mostrou densidades endoteliais superiores e perdas de células endoteliais inferiores ao DSAEK nos primeiros 15 meses de seguimento, mas as determinações posteriores foram semelhantes nos dois grupos. Assim, as duas técnicas apresentaram densidades endoteliais e perda de células endoteliais a longo prazo semelhantes entre si, pelo que outros critérios devem ser usados para determinar qual a técnica mais adequada para cada caso na nossa prática clínica.Purpose: To compare endothelial cell loss in adult patients with corneal endothelial disorders who were submitted to Descemet stripping automated endothelial keratoplasty (DSAEK) or Descemet membrane endothelial keratoplasty (DMEK). Methods: Retrospective, single-centre, observational cohort study. 51 eyes from 51 patients that underwent DSAEK (n=23 patients) or DMEK (n=28 patients) at Centro Hospitalar Universitário S. João (Porto, Portugal), between April 2015 and March 2020 were included. Patients without at least one endothelial cell density (ECD) determination after transplantation and those who experienced primary graft failure were excluded. Patient demographics, best corrected visual acuity (BCVA) with the logMAR scale before and one year after grafting, indication for transplantation, and postoperative complications were recorded. Specular microscopy with ECD determination (in cells/mm2) was performed on all donor corneas before grafting and regularly after transplantation. Results: Patients' demographics, indications for transplantation and BCVA before grafting were similar in both groups. BCVA 1-year after transplantation was better in the DMEK group (0.26 ± 0.19 vs. 0.47 ± 0.29 in the DSAEK group; p=0.003). ECD in donor corneas before grafting was similar in both groups (p=0.986). Graft ECD after transplantation was higher in the DMEK group at up to 5 months (p<0.001), 5 to 9 months (p=0.037) and 9 to 15 months follow-up (p=0.003), being similar in posterior determinations. ECD loss was lower in the DMEK group at up to 5 months (p<0.001), 5 to 9 months (p=0.004) and 9 to 15 months follow-up (p=0.016), being similar in posterior determinations. 2 DMEK eyes required rebubbling. 2 DSAEK eyes suffered graft rejection. Conclusion: In our cohort, DMEK presented better visual outcomes than DSAEK. The DMEK group showed higher mean ECD and lower ECD loss in the first 15 months of follow-up, but posterior measurements were similar in both groups. Therefore, both techniques had similar long-term mean ECD and ECD loss and other criteria should be used to determine which one is best suited for each case in our clinical practice.