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Rossaak, Jeremy Ian, and n/a. "The genetics of abdominal aortic aneurysms." University of Otago. Dunedin School of Medicine, 2004. http://adt.otago.ac.nz./public/adt-NZDU20070502.143818.
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Abdominal Aortic Aneurysms (AAA) are amongst the top ten most common cause of death in those over 55 years of age. The disease is usually asymptomatic, often being diagnosed incidentally. Once diagnosed, elective repair of an AAA results in excellent long-term survival with a 3-5% operative mortality. However, up to one half of patients present with ruptured aneurysms, a complication that carries an 80% mortality in the community, and of those reaching hospital, a 50% mortality. Clearly early diagnosis and treatment results in improved survival.
Screening for AAA, with ultrasound, would detect aneurysms early, prior to rupture. However, debate continues over the cost effectiveness of population based screening programmes. The identification of a sub-population at a higher risk of developing AAA would increase the yield of a screening prograrmne. A number of populations have been examined, none of which have received international acceptance.
About 20% of patients with an AAA have a family history of an aneurysm. The disease is also considered to be a disease of Caucasians, both facts suggesting a strong genetic component to the disease. Perhaps a genetically identified sub-population at a high risk of developing an AAA would prove to be an ideal population for screening.
This thesis examines the incidence of aneurysms and the family histories of patients with AAA in the Otago region of New Zealand. Almost twenty percent of the population has a family history of AAA. DNA was collected from each of these patients for genetic analysis. The population was divided into familial AAA and non-familial AAA for the purpose of genetic analysis and compared to a control population.
AAA is believed to be a disease of Caucasians; a non-Caucasian population with a low incidence of AAA may prove to be a good control population for genetic studies. A literature review demonstrated a higher incidence of AAA in Caucasians than other ethnic groups and within Caucasians a higher incidence in patients of Northern European origin. The incidence was low in Asian communities, even in studies involving of migrant Asian populations. The New Zealand Maori are believed to have originated from South East Asia, therefore could be expected to have a low incidence of AAA and would make an ideal control population for genetic studies. A pilot study was undertaken to examine the incidence of AAA in the New Zealand Maori. The age standardised incidence of AAA proved to be at least equal in Maori to non-Maori, with a more aggressive form of the disease in Maori, manifesting with a younger age at presentation and a higher incidence of ruptured aneurysms at diagnosis.
It is well known that at the time of surgery, an AAA is at the end stage in its life. At this time, inflammation and matrix metalloproteinases (MMP) enzymes are prevalent within the aneurysm wall and have destroyed the wall of the aorta. One of the most important genetic pathways regulating these enzymes is the plasminogen activator inhibiter 1-Tissue plasminogen activator-plasmin pathway.
Genetic analysis of this pathway demonstrated an association of the 4G5G polymorphism in the promoter of the PAl-1 gene with familial AAA. In this insertion:deletion polymorphism, the 5G variant binds an activator and repressor, resulting in reduced PAI-1 expression and ultimately increased MMP activation. This allele was associated with familial aneurysms, 47% versus 62% non-familial AAA and 61% controls (p=0.024).
A polymorphism within the tissue plasminogen activator gene was also examined and no association was found with AAA.
Another way the MMPs expression could be increased is from mutations or polymorphisms in their own genetic structure. Stromelysin 3 is itself a MMP capable of destroying the aortic wall and it has a role in activating other MMPs. A 5A6A insertion:deletion polymorphism exists in the promoter of this gene. The 5A allele variant results in increased stromelysin expression and is associated with AAA 46% versus 33% in controls p=0. 0006.
The actions of the MMPs are themselves inhibited by the tissue inhibitors of matrix metalloproteinases. The TIMP genes have been sequenced; two polymorphisms have been identified in the non-coding promoter area of the TIMP 1 gene. Further studies are necessary to examine the effect of these polymorphisms.
Inflammation has been implicated in aneurysm progression. One of the roles of the inflammatory cells found in an aneurysm is to deliver the MMP�s to the AAA. The HLA system is integral in controlling this inflammation and was therefore examined.
From this series of studies it is concluded that there is a genetic component to AAA. This thesis presents the first genetic polymorphism associated with familial AAA and explores the role of a genetic pathway in the formation of AAA.
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Norrgård, Örjan. "Familial occurrence of abdominal aortic aneurysms." Doctoral thesis, Umeå universitet, Kirurgi, 1985. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-100555.
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The occurrence of clinically diagnosed and/or ruptured abdominal aortic aneurysms (AAAs) in the families of 220 patients with AAAs, treated at the Surgical Clinic, University Hospital of Umeå in the northern part of Sweden during the years 1965-82, was studied. A questionnaire concerning the blood relatives was answered by 87/89 patients. 16/87 patients (18%) had blood relatives with AAAs. In 14 families one blood relative was affected, and in 2 families two blood relatives were affected. First degree relatives were affected in 9/87 cases (10%), and second degree relatives in 7/87 cases (8%). 9/468 (1.9%) of the patients' brothers and sisters but only five of all their cousins had AAAs, and 7/204 (3.4%) of the dead brothers and sisters had died of ruptured AAAs. Concerning the patients who were not included in the letter survey at least 14/133had blood relatives with AAAs. However, the great majority of these patients were dead when the study was performed and could not be asked aboutthe occurrence of AAAs in their families. The patients with AAAs had significantly higher serum concentrations of triglyceride and (YLDL + LDL)-cholesterol and a significantly lower serum concentration of HDL-cholesterol than randomly selected healthy controls of the same sex and age as the patients. We also compared the distributions of genetic markers (HLA antigens, the blood group systems ABO, Rh, MNSs, P, Kell, Lewis and Duffy and the serum protein group systems haptoglobin, transferrin, group-specific component, complement C3, properdin factor and alpha-1-antitrypsin) in patients with AAAs with the distributions in controls and in some cases with the expected distributions according to the Hardy-Weinberg law. A significantly decreased frequency of Rh-negative individuals, and significantly increased frequencies of Kell-positi ve individuals, of MN heterozygotes and of heterozygotes concerning haptoglobin type was found. Furthermore, the aneurysm walls of patients with and without AAAs in the family were compared concerning the morphology, but no differences were found. We also studied the occurrence of collagen types I and III in the aneurysm walls, and the occurrence of vimentin and desmin in the smooth muscle cells of the aneurysm walls, but all these components were present in the aneurysm walls of both the patients with and those without AAAs in the family. To summarize the results, there seems to be an increased frequency of AAAs, and especially of ruptured AAAs, among the brothers and sisters of patients with AAAs. Elevated serum concentrations of triglyceride and (VLDL + LDL)- cholesterol and a lowered serum concentration of HDL-cholesterol seems to be common in patients with AAAs. There seems to be a hereditary predisposition to the development of AAAs, because we found associations with four different genetic markers (Rh, MN, Kell, haptoglobin group). However, there is probably no specific "familial" type of AAAs, because we found no differences between the patients with and those without AAAs in the family.Key words:S. 1-42: sammanfattning, s. 43-103: 5 uppsatser
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Polzer, Stanislav. "Stress-Strain Analysis of Aortic Aneurysms." Doctoral thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2012. http://www.nusl.cz/ntk/nusl-234135.
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Tato práce se zabývá problematikou aneurysmat břišní aorty a možností využít konečnoprvkovou deformačně-napěťovou analýzu těchto aneurysmat ke stanovení rizika ruptury. První část práce je věnována úvodu do problematiky, popisu kardiovaskulární soustavy člověka s důrazem na abdominální aortu, anatomii, fyziologii a patologii stěny tepny s důrazem na procesy vedoucí ke vzniku aneurysmatu. Dále se práce věnuje rizikovým faktorům přispívajících ke vzniku aneurysmat spolu s analýzou současných klinických postupů ke stanovení rizika ruptury spolu se srovnáním navrhovaného kritéria maximálního napětí. Dominantní část této disertace je věnována identifikaci faktorů ovlivňujících napjatost a deformaci stěny aneurysmatu spolu s návrhem nových postupů, prezentací vlastních poznatků vedoucích ke zpřesnění určení rizika ruptury pomocí deformačně- napěťové analýzy a metody konečných prvků. Nejprve je analyzován vliv geometrie, vedoucí k závěru, že je nezbytné používání individuálních geometrií pacienta. Dále je pozornost zaměřena na odbočující tepny, které ve stěně působí jako koncentrátor napětí a mohou tedy ovlivňovat napjatost v ní. Jako další podstatný faktor byl identifikován vliv nezatížené geometrie a bylo napsáno makro pro její nalezení, které bylo opět zahrnuto jako standardní součást do výpočtového modelu. Mechanické vlastnosti jak stěny aneurysmatu, tak intraluminálního trombu jsou experimentálně testovány pomocí dvouosých zkoušek. Také je zde analyzován vliv modelu materiálu, kde je ukázáno, že srovnávání maximálních napětí u jednotlivých modelů materiálu není vhodné díky zcela rozdílným gradientům napětí ve stěně aneurysmatu. Dále je zdůrazněna potřeba znalosti distribuce kolagenních vláken ve stěně a navržen program k jejímu získání. Intraluminální trombus je analyzován ve dvou souvislostech. Jednak je ukázán vliv jeho ruptury na napětí ve stěně a jednak je analyzován vliv jeho poroelastické struktury na totéž. Posledním identifikovaným podstatným faktorem je zbytková napjatost ve stěně. Její významnost je demonstrována na několika aneurysmatech a i tato je zahrnuta jako integrální součást do našeho výpočtového modelu.Na závěr jsou pak navrženy další možné směry výzkumu.
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Nordon, Ian Michael. "Mining the proteome of abdominal aortic aneurysms." Thesis, St George's, University of London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.546777.
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Forester, Nerys Dawn. "Mechanisms of inflammation in abdominal aortic aneurysms." Thesis, University of Leeds, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.417894.
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Koenig, Sara Nichole. "Investigation of Notch1 Functions in Aortic Valve Disease and Ascending Aortic Aneurysms." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1480641922918658.
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Malina, Martin. "Endovascular repair of abdominal aortic aneurysms aspects on a novel technique /." Lund : Dept. of Vascular and Renal Diseases, Lund University, Malmö University Hospital, 1998. http://books.google.com/books?id=hWBsAAAAMAAJ.
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Huusko, T. (Tuija). "Genetic and molecular background of ascending aortic aneurysms." Doctoral thesis, Oulun yliopisto, 2013. http://urn.fi/urn:isbn:9789526201269.
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Abstract Thoracic aortic aneurysms (TAAs) are a significant source of morbidity and mortality. Classical risk factors for TAAs are hypertension, atherosclerosis, male gender, smoking, age, high body mass index, family history and chronic obstructive pulmonary disease. In addition, in certain cases of TAAs, i.e., ascending aortic aneurysms (AscAA), genetic factors are highly prominent. Matrix metalloproteinases are in a major role in the destruction of the aortic wall and the imbalance between matrix metalloproteinases, and their inhibitors are involved in the formation of aneurysms. In addition, osteopontin is a potent regulator of matrix metalloproteinases and it is widely expressed in injured arteries. Recently, telomere shortening has been shown to be involved in the development of abdominal aortic aneurysms (AAA). In this aneurysm type, atherosclerosis has a major role. Since atherosclerosis is frequently absent in the case of TAAs, the length of telomeres was measured in the blood samples of TAA patients. The purpose of this thesis was to study the genetic background of TAAs of the ascending aorta and furthermore, the molecular background of this disease. The first study was done with families with TAAs, and dissections and one chromosomal locus (5q13-14) of the studied seven loci showed a significant genetic linkage for TAAs. Two other studies were done exploiting our TAA case-control material. Study II showed elevated levels of osteopontin, matrix metalloproteinase type 2 and 9 in the plasma and tissue samples of TAA patients compared with controls. In the third study, longer blood leukocyte telomeres were found in the DNA samples of TAA patients compared with controls; furthermore, the elevation of telomere lengthening protein telomerase expression was found in the tissue samples of TAA patients. This thesis presents region 5q13-14 as a potential genetic regulator for TAAs in Finnish families. In addition, elevated levels of osteopontin, matrix metalloproteinase type 2 and 9 can be considered as a plasma biomarker for aneurysmal disease. Furthermore, longer blood leukocytes were found to be a significant risk factor for developing TAAsTiivistelmä Rinta-aortan aneurysmat ovat merkittävä sairastumisiin ja kuolemiin johtava tekijä. Perinteisinä riskitekijöinä aneurysmille on pidetty korkeaa verenpainetta, ateroskleroosia, miessukupuolta, tupakointia, ikää, ylipainoa, suvussa esiintyneitä aneurysmatapauksia ja keuhkoahtaumatautia. Näiden lisäksi erityisesti nousevan rinta-aortan alueella esiintyvissä aneurysmissa myös perinnöllisillä tekijöillä on korostunut merkitys. Matriksimetalloproteinaaseilla ja niiden estäjillä on merkittävä rooli, kun aortan seinämää hajotetaan. Tasapainon järkkyminen kyseisten proteiinien keskinäisessä suhteessa voi johtaa aneurysman muodostumiseen. Myös osteopontiinin tiedetään olevan tehokas matriksimetalloproteinaasien säätelijä, ja sitä tuotetaankin yleisesti vahingoittuneessa verisuonessa. Telomeerien lyhentyminen on vastikään yhdistetty vatsa-aortan alueella esiintyviin aneurysmiin, joissa ateroskleroosilla on yleensä merkittävä rooli. Koska ateroskleroosi on vain harvoin nousevan rinta-aortan alueen aneurysmien taustalla, rinta-aortan aneurysmapotilaiden valkosolujen telomeerien suhteelliset pituudet määritettiin. Väitöskirjan ensimmäisessä osatyössä keskityttiin löytämään geneettinen kytkentä rinta-aortan aneurysmien ja jonkin seitsemän tutkitun kromosomialueen välille. Geneettinen kytkentä löydettiin kromosomialueelta 5q13-14. Osatöissä 2 ja 3 hyödynnettiin rinta-aortan aneurysmien potilas- ja verrokkiaineistoja. Osatyö 2 osoitti, että matriksimetalloproteinaasien (2 ja 9) määrät ovat kohonneet rinta-aortan aneurysmapotilaiden näytteissä verrokkeihin verrattuna. Osatyössä 3 telomeerien suhteelliset pituudet veren valkosoluissa olivat pidemmät nousevan rinta-aortan aneurysmapotilaiden näytteissä verrokkihenkilöiden näytteisiin verrattuna. Myös telomeraasin tuotto oli lisääntynyt rinta-aortan aneurysmapotilaiden aorttakudosnäytteissä. Väitöskirjassa esitetään tuloksena kromosomialue 5q13-14 geneettisenä säätelijänä suomalaisissa suvuittain esiintyvissä rinta-aortan aneurysmatapauksissa. Kohonneita matriksimetalloproteinaasien ja osteopontiinin tasoja voidaan lisäksi pitää biomarkkereina rinta-aortan aneurysmien sairastavuudelle. Veren valkosolujen pidemmät telomeerit näyttävät myös olevan yhteydessä rinta-aortan aneurysmien sairastavuuteen
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Nasim, Akhtar. "Evaluation of endovascular repair of abdominal aortic aneurysms." Thesis, University of Leicester, 1997. http://hdl.handle.net/2381/29600.
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Initially a retrospective study was undertaken to assess the current abdominal aortic aneurysm practice in terms of workload, mortality, complications and risk factors, to assess whether there is a role for endovascular AAA repair in Leicester. Then an experimental animal model was developed to investigate the necessity for anchoring the distal end of the graft with a second stent, the effect of placing stents across the renal ostia, and whether inferior mesenteric or lumbar artery backbleeding persists into the excluded aneurysm sac. A study has also been performed to assess the clinical application of this technique. A prospective study was undertaken in 82 consecutive patients referred for elective aneurysm repair to determine the best imaging modality for pre-operative assessment prior to endovascular AAA repair. A comparison was made between computed tomography (CT), magnetic resonance angiography (MRA), colour duplex and intra-arterial digital substraction angiography (IA-DSA). The morphology of the aneurysm in these patients was assessed to determine the proportion of patients that may benefit from this technique. Finally, the preliminary clinical experience with 3 different endoluminal grafts, one of which was developed in this study, was assessed. The results presented in this thesis show that work load of AAAs in Leicester has slowly increased over the past decade but there has been no significant improvement in the mortality figures for elective and emergency aneurysm surgery during this period. The results of the animal work show that a distal stent is necessary for complete exclusion of the aneurysm sac, but the safety of deploying stents across the renal arteries remains uncertain. This study also shows that MRA provides the best non-invasive assessment of aneurysm morphology prior to endovascular repair when compared to CT and IA-DA (p < 0.01).
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Xu, Dong. "Genetic factors and phenotypic variability in Marfan syndrome and abdominal aortic aneurysm /." [St. Lucia, Qld.], 1999. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16256.pdf.
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Hannuksela, Matias. "Familial thoracic aortic aneurysms and dissections : studies on genotype and phenotype." Doctoral thesis, Umeå universitet, Anestesiologi och intensivvård, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-134028.
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Background: Thoracic aortic aneurysms and dissections (TAAD) have a genetic component with an estimated 20-25% of the patients having a positive family history. An aneurysm often precedes a dissection. Acute aortic dissections are associated with high mortality and morbidity, even when operated on. Complications due to prophylactic surgery are considerably fewer. Therefore, patients at risk for dissection should be identified, followed-up and evaluated for prophylactic intervention. Aims: 1. To establish reference values for ascending (AoA) and descending aortic (AoD) diameters measured by computed tomography. 2. To study the effectiveness of phenotypic cascade screening in families with an inherited form of thoracic aortic aneurysms and dissections (FTAAD) and to address questions that arise when screening for a genetic disorder is applied. 3. To study the agreement of aortic diameters obtained by TTE and MRI and to study aortic stiffness in individuals from families with FTAAD. 4. To perform exome sequencing in order to identify pathogenic sequence variants causing FTAAD, to characterize the phenotype, and to compare thoracic aortic diameter and stiffness in mutation carriers and non-carriers. Results: Paper I: The diameter of the thoracic aorta increased by 0.17 mm (0.12 – 0.20 mm) per year. The mean sex-related difference in diameter was 1.99 mm (1.28 – 2.60 mm) with men having larger aortas than women. The mean difference in aortic diameter per unit BMI was 0.27 mm (0.14 – 0.44 mm). Upper normal limits for the AoA can be calculated by the formula D (mm)=31+0.16*age and for the AoD by D (mm)=21+0.16*age. Paper II: Of 106 individuals from families with FTAAD but without known thoracic aortic disease, 19 individuals (18%) were identified to have a dilated AoA. The expected number of individuals in this group with an autosomal dominant disease would have been 40 (p<0.0001). In first-degree relatives younger than 40, we found only one individual with a dilated aorta although the expected number of individuals with disease causing mutation would have been 10. Paper III: Of 116 individuals investigated, 21 were identified with thoracic aortic dilatation and 95 individuals with normal thoracic aortic diameter. Aortic stiffness increased with age and diameter. The individuals with aortic dilatation were older than those without (49 vs. 37 years, p=0.001) and showed lower aortic elastic properties. The diameters measured by TTE and MRI correlated strongly (r2=0.93). The mean difference in diameters between the two methods was 0.72 mm (95% CI 0.41-1.02) with TTE giving larger diameters than MRI. Paper IV: From exome sequencing and segregation analysis, a 2-bp deletion in the MYLK gene (c.3272_3273del) was identified to cause FTAAD. The age and the aortic diameter at dissection or rupture varied in the family members. We did not find any differences in aortic diameter, aortic stiffness, or pulse wave velocity between carriers and non-carriers. Conclusions: Thoracic aortic diameter increases with age, and sex and body size are also associated with the diameter. In FTAAD, screening identifies family members with a previously unknown aortic dilatation. However, a normal aortic diameter does not exclude an individual from being a carrier of FTAAD. TTE can be used in follow-up for the ascending aorta. Individuals identified to have a dilated thoracic aorta have increased aortic stiffness compared to individuals with normal thoracic aortic diameter. The MYLK mutation (c.3272_3273del) causes thoracic aortic dissections with variable clinical expression. No differences in aortic stiffness were identified between MYLK mutation carriers and non-carriers.
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Gopalakrishnan, Shyam Sunder. "Dynamics and Stability of Flow through Abdominal Aortic Aneurysms." Doctoral thesis, Université de Lyon 1, Ecole Centrale de Lyon, Lyon, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/245358.
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Peppelenbosch, Arnoud Gerardus. "Endovascular treatment in elective and ruptured abdominal aortic aneurysms." [Maastricht : Maastricht : Maastricht University] ; University Library, Universiteit Maastricht [host], 2007. http://arno.unimaas.nl/show.cgi?fid=12755.
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Dawson, Joseph Allard. "Investigations into the medical management of abdominal aortic aneurysms." Thesis, St George's, University of London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511900.
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Malkawi, Amir H. "Wall stress dependent gene espression in abdominal aortic aneurysms." Thesis, St George's, University of London, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558352.
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Patient specific wall stress analysis demonstrated that wall stress was higher in AAA's at risk of rupture. Furthermore, there is a correlation between sites of rupture and high wall stress regions. We set out to investigate the gene expression in regions of high and low wall stress to identify the role of wall stress in the pathogenesis of AAA Methods Finite element analysis (PEA, ADINA R&D Inc., Watertown, USA) was performed on patients with AAA scheduled for open repair. Regions of high and low wall stress were identified from the obtained patient specific wall stress map. Coordinates of regions of high and low stress were mapped on a three-dimensional reconstruction of each aneurysm which included major visceral branches as reference points to aid in intra-operative localization. High and low stress regions were marked intra-operatively on the aneurysm surface according to their distance from the reference points and full-thickness biopsies were obtained. RNA was extracted (RNeasy Fibrous Tissue RNA Extraction Kit, Qiagen, UK) and whole genome profiling was performed (Illurnina HumanRef-8 v3.0 Expression BeadChips). Protein expression was determined by Western blotting. Results PEA was performed on 11 patients. Paired samples were obtained from high and low wall stress regions. AAA wall was found to be thinner in regions exposed to high wall stress. There was over-expression of LMNA (Larnin AlC) in high wall stress regions. Over-expression of lamin AlC was also demonstrated on Western blotting. Conclusion Our results identify novel pre-rupture changes in AAA's in regions exposed to high stress. This is the first study to identify a role for lamin AlC in AAA pathogenesis. Over expression of lamin A/C in high wall stress regions highlights the role of cytoskeletal and nuclear mechanics, mechanotransduction and apoptotic transcriptional pathways in AAA development and rupture.
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Rayt, Harjeet Singh. "An investigation into candidate genes for abdominal aortic aneurysms." Thesis, University of Leicester, 2013. http://hdl.handle.net/2381/37195.
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There is growing evidence to suggest that abdominal aortic aneurysm (AAA) is a complex disease with multiple environmental and genetic risk factors. Susceptibility genes have been investigated through multiple underpowered candidate gene studies, which has led to the association of numerous genes with conflicting evidence. This study aimed to investigate the commonly cited associations between polymorphisms of the matrix metalloproteinase-9; MMP9(-1562C > T), tissue inhibitor of metalloproteinase-1; TIMP1(+434C > T) and TIMP1(rs2070584), platelet activating factor acetylhydrolase; PLA2G7(- 994G > T), estrogen receptor beta; ESR2(+1730 A-G) and Heme oxygenase 1; HMOX1(GT)n genes and AAA in a large powered study to provide definitive evidence of any association. Materials & Methods: A case-control study was performed of 1,202 patients with AAA and 1,059 screened control subjects. DNA was extracted from whole blood and genotyping was performed using polymerase chain reaction based restriction fragment length polymorphisms (PCR-RFLP). Results Two polymorphisms (ESR2 (OR 1.42, P < 0.0001) and HMOX1 (OR 1.99, P < 0.0001)) showed a potential association with AAA. One polymorphism (TIMP1 rs2070584) could not be genotyped despite using 2 different methods. Polymorphisms of the MMP9 (OR 0.99, P=0.82), PLA2G7 (OR 0.76, P=0.29) and TIMP1 (+434C > T) (OR 0.94, P=0.46) genes did not show an association with AAA. Conclusion: We have demonstrated an association between polymorphisms of the ESR2 and HMOX1 genes and AAA, although further work is essential to confirm this association. Contrary to other published data, no such association was seen in common polymorphisms of the MMP9, TIMP1, and PLA2G7 genes and AAA.
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Hardman, David. "Computational modelling of monocyte deposition in abdominal aortic aneurysms." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5585.
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Abdominal aortic aneurysm (AAA) disease involves a dilation of the aorta below the renal arteries. If the aneurysm becomes sufficiently dilated and tissue strength is less than vascular pressure, rupture of the aorta occurs entailing a high mortality rate. Despite improvements in surgical technique, the mortality rate for emergency repair remains high and so an accurate predictor of rupture risk is required. Inflammation and the associated recruitment of monocytes into the aortic wall are critical in the pathology of AAA disease, stimulating the degradation and remodeling of the vessel wall. Areas with high concentrations of macrophages may experience an increase in tissue degradation and therefore an increased risk of rupture. Determining the magnitude and distribution of monocyte recruitment can help us understand the pathology of AAA disease and add spatial accuracy to the existing rupture risk prediction models. In this study finite element computational fluid dynamics simulations of AAA haemodynamics are seeded with monocytes to elucidate patterns of cell deposition and probability of recruitment. Haemodynamics are first simulated in simplified AAA geometries of varying diameters with a patient averaged flow waveform inlet boundary condition. This allows a comparison with previous experimental investigations as well as determining trends in monocyte adhesion with aneurysm progression. Previous experimental investigations show a transition to turbulent flow occurring during the deceleration phase of the cardiac cycle. There has thus far been no investigation into the accuracy of turbulence models in simulating AAA haemodynamics and so simulations are compared using RNG κ − ε, κ − ω and LES turbulence models. The RNG κ − ε model is insufficient to model secondary flows in AAA and LES models are sensitive to inlet turbulence intensity. The probability of monocyte adhesion and recruitment depends on cell residence time and local wall shear stress. A near wall particle residence time (NWPRT)model is created incorporating a wall shear stress-limiter based on in vitro experimental data. Simulated haemodynamics show qualitative agreement with experimental results. Peaks of maximum NWPRT move downstream in successively larger geometries, correlating with vortex behaviour. Average NWPRT rises sharply in models above a critical maximum diameter. These techniques are then applied to patient-specific AAAs. Geometries are created from CT slices and velocity boundary conditions taken from Phase Contrast-MRI (PC-MRI) data for 3 patients. There is no gold standard for inlet boundary conditions and so simulations using 3 velocity components, 1 velocity component and parabolic flow profiles at the inlet are compared with each other and with PC-MRI data at the AAA midsection. The general trends in flow and wall shear stress are similar between simulations with 3 and 1 components of inlet velocity despite differences in the nature and complexity of secondary flow. Applying parabolic velocity profiles, however, can cause significant deviations in haemodynamics. Axial velocities show average to good correlation with PC-MRI data though the lower magnitude radial velocities produce high levels of noise in the raw data making comparisons difficult. Patient specific NWPRT models show monocyte infiltration is most likely at or around the iliac bifurcation.
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Stather, Philip William. "The differential expression of microrna in abdominal aortic aneurysms." Thesis, University of Leicester, 2014. http://hdl.handle.net/2381/29257.
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Abdominal aortic aneurysms (AAA) account for 5,251 deaths per year in the UK (2010). Their current incidence in the NHS AAA screening programme is 1.8%, however the vast majority are small. These patients therefore undergo surveillance prior to the need for surgical intervention. Biomarkers for AAA have been extensively studied, with a meta-analysis, conducted herein, identifying a significant association between several biomarkers and AAA (upregulation of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1, interleukin-6, interleukin-10, tumour necrosis factor-α, osteoprotegerin, osteopontin, interferon-γ, intercellular adhesion molecule-1, vascular cell adhesion protein-1, D-dimer, C-reactive protein, alpha-1 antitrypsin, fibrinogen, triglycerides, and lipoprotein(a), and downregulation of apolipoprotein-A and high density lipoprotein). However, the sensitivity and specificity of these biomarkers is poor, therefore this thesis aimed to look at the expression of microRNAs (miRNAs) in AAA, hitherto previously unstudied. MiRNAs are short, non-coding RNA sequences which are transcribed from DNA, however they are not translated into protein. They exert their effect by attaching to messenger RNA (mRNA) and causing repression of translation into protein, and deadenylation, thus causing mRNA degradation. MiRNAs are capable of interacting with over 60% of known genes. The studies within this thesis have undertaken a case control discovery and validation study into miRNAs in AAA, identifying a significant upregulation of 29 miRNAs within the discovery study, 4 of which were validated in blood (let-7e, miR-15a, miR-196b, miR-411), and miR-196b being further validated in plasma. There was however no miRNA dysregulation found in aortic tissue. In addition, these 4 miRNAs were found to have significant interactions with previously studied AAA biomarkers identified through earlier systematic review and meta-analysis. The 4 miRNAs identified within this thesis were similarly dysregulated in patients with peripheral arterial disease, therefore they may be dysregulated due to generalised atherosclerosis rather than AAA, and must be interpreted with caution.
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Wild, John Benjamin. "An investigation into genetic polymorphisms and abdominal aortic aneurysms." Thesis, University of Leicester, 2015. http://hdl.handle.net/2381/38838.
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Introduction: A wide variety of genetic polymorphisms have demonstrated a significant association to the disease abdominal aortic aneurysm (AAA). Polymorphisms in rs217120 (Cathepsin C gene CTSC) and rs1466535 (low density lipoprotein receptor related protein 1 gene, LRP1) have both been associated with AAA, rs1466535 from a genome wide association study (GWAS). Materials & Methods: Associations were first confirmed then exons in close proximity to the polymorphisms were re-sequenced in order to detect new mutations. Protein levels were assayed and tissue was stained in order to determine the arterial layer that the LRP1 protein resides within. TaqMan genotyping was undertaken in order to determine allele frequency of the SNPs of interest in cohorts from Belfast (211 AAA, 262 controls), Viborg (473 AAA, 195 controls), Leeds (214 AAA and 249 controls) and Leicester (266 AAA, 143 controls). Subsequently a list of linked SNPs was generated and the same samples were analysed in order to fine map the gene(s) of interest. Samples from Leicester (96 AAA, 96 controls) were sequenced. Serum protein concentrations were measured with an ELISA (43 AAA, 26 controls). Immunohistochemical analysis of aortic biopsies (n = 6) was also performed. Results: rs217120 failed to associate with AAA in 3 of 4 the replication cohorts and meta-analysis of all data was also not significant, odds ratio 1.17 (95% Confidence Interval 0.98-1.39), P value = 0.08. rs1466535 did not significantly associate with AAA in the replication cohorts however when the data was meta-analysed with the discovery phase of the GWAS (1866 AAA, 5435 controls) the association was significant, odds ratio 1.23 (95% Confidence Interval 1.14-1.33), P value 1.25x¹⁰⁻⁷. A second SNP within LRP1, rs11172114, was found to have a more significant association, odds ratio 1.23 (95% Confidence Interval 1.14 to 1.31), P value 3.87x¹⁰⁻⁸. Re-sequencing of the 3 LRP1 exons did not detect any novel mutations. Serum LRP1 levels between cases and controls were not different (mean concentration 583.4 v 631.3ng/ml, P value = 0.69). There was also no significant difference when samples were analysed by SNP genotype, rs1466535 P value = 0.07. Analysis of aortic tissue biopsies did not determine an association between LRP1 genotype and cellular location. Conclusion: SNPs within LRP1 associate with AAA, with rs11172114 being most significant. However the polymorphism is not associated with protein levels in serum and is not clearly localizing to any given layer of the arterial wall. More investigation is required to determine how LRP1 affects aneurysm development and growth.
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Magnuson, Cody A. "Pharmacologic Treatment of Ascending Aortic Aneurysms in Notch1+/- Mice." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1555070671699082.
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Ashton, John Hardy. "Polymeric Endo-Aortic Paving (PEAP): Initial Development of a Novel Treatment for Abdominal Aortic Aneurysms." Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/204293.
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Abdominal aortic aneurysm (AAA) is a prevalent disease in developed countries. While endovascular aneurysm repair is fairly successful, it has shortcomings. Polymeric endoluminal paving and sealing is a method that has previously been developed to treat a range of diseases. Our goal is to further develop this technique to treat AAA, a process we have named polymeric endo-aortic paving (PEAP). We hypothesize that PEAP will overcome many of the limitations associated with EVAR by providing a minimally invasive treatment which can be used on patients with complicated AAA geometries and reducing incidence of migration and endoleak. Additionally, we plan to incorporate drug delivery into PEAP to improve efficacy. The purpose of this work was to evaluate a potential graft material for PEAP and to develop a thrombus mimic which will aid in further PEAP development. Blends of polycaprolactone/polyurethane (PCL/PU) were assessed by characterizing their mechanical, thermoforming, and degradation properties. PCL/PU grafts have a similar stiffness to aortic tissue and can be thermoformed at temperatures approaching 37 degrees C. Blending PCL with PU significantly reduces PCL's degradation. An anisotropic hyperelastic strain energy function was developed for the PCL/PU blends and finite element modeling (FEM) was used to show that stress reduction on the AAA wall that can be achieved by PEAP is similar to current EVAR. Stiffness varies throughout the AAA thrombus, and thrombus mimics were developed that have similar stiffness, components, and structure to native AAA thrombus.
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Mukherjee, Kamalika. "ROLE OF CYCLOOXYGENASE-2 IN ABDOMINAL AORTIC ANEURYSMS IN MICE." UKnowledge, 2012. http://uknowledge.uky.edu/pharmacy_etds/29.
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Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease with no available pharmacological treatment. AAA formation reduces the structural integrity of the vessel and increases the susceptibility to rupture. The inflammatory response within human aneurysmal tissue is characterized by increased expression of cyclooxygenase-2 (COX-2). Similarly, in a mouse model of the disease induced by chronic Angiotensin II (AngII) infusion, we have shown that COX-2 expression in the abdominal aortic smooth muscle layer increases early in the development of the disease. Furthermore, genetic or pharmacological inactivation of COX-2 prior to disease initiation reduces AAA incidence.
The current study utilized nonhyperlipidemic mice to determine the effectiveness of COX-2 inhibition initiated after AAA formation. COX-2 inhibitor treatment was initiated 5 days after beginning the AngII infusion, a time-point where significant aneurysmal pathology is observed. COX-2 inhibition with celecoxib significantly reduced the incidence as well as severity of AAAs as compared to the control group. Celecoxib treatment also protected the mice from aortic rupture and death. AAA development is characterized by degradation of the aortic smooth muscle layer with loss of the contractile phenotype. We found that the effectiveness of celecoxib was associated with significantly increased mRNA expression of alpha-actin, SM22alpha and desmin, all of which are markers of a differentiated smooth muscle cell phenotype. Celecoxib treatment also decreased mRNA expression of a marker of dedifferentiated smooth muscle (hyaluronic acid synthase 2). We also examined the role of altered expression of COX-2 in the increased susceptibility of the abdominal segment to AAA formation. We found a prolonged and greater induction of COX-2 in the abdominal aortic smooth muscle layer in contrast to a transient induction of COX-2 in the other regions of the aorta throughout disease progression. Overall, these findings suggest that COX-2 plays an important role in AAA development in mice, and COX-2 inhibition with celecoxib attenuates progression of aneurysm development by maintaining a differentiated phenotype in abdominal aortic smooth muscle cells.
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Goodson, Robert Andrew Hawksley. "Analysis of growth and rupture of fusiform abdominal aortic aneurysms." Thesis, Nottingham Trent University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341287.
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Toghill, Bradley James. "Investigating the role of DNA methylation in abdominal aortic aneurysms." Thesis, University of Leicester, 2018. http://hdl.handle.net/2381/42484.
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Abdominal aortic aneurysm (AAA) is a complex disease characterised by the irreversible dilation of the abdominal aorta. Little is known about its epigenetic basis, and DNA methylation is the most extensively studied epigenetic mechanism. Global methylation was assessed in peripheral blood mononuclear cell (PBMC) DNA from 185 people using enzyme-linked immunosorbent assays (ELISAs), identifying global hypermethylation in those with a large AAA, and a linear association with increasing AAA diameter. The regulatory regions of genes proximal to AAA genomic risk loci were then bisulphite sequenced using next-generation sequencing (NGS) in PBMC DNA from 96 people and vascular smooth muscle cell (VSMC) DNA from 44 people. In PBMCs, hypermethylation in individuals with AAA was seen in LDLR, SORT1 and IL6R. In VSMCs, the same region in IL6R was hypermethylated and differential methylation was also observed in ERG, SERPINB9, and SMYD2. ELISAs were conducted on plasma from the same PBMC samples to corroborate the methylation patterns seen in LDLR, IL6R and SORT1, where there was a reduction in circulating IL6R. Gene expression analysis was also performed on mRNA from the VSMCs. SERPINB9 was downregulated in AAA but independently of DNA methylation, and a relationship between SMYD2 promoter hypo-methylation and decreased SMYD2 gene expression was shown. Downregulation of SMYD2 in AAA was further corroborated in 6 whole aortic tissue samples using immunohistochemistry. This PhD has illustrated a significant original contribution to knowledge at each stage. Global and gene specific DNA methylation changes are associated with AAA and could be involved in disease pathobiology. This is the first work to assess DNA methylation in AAA using NGS, and the first to assess methylation in VSMCs. In particular, methylation status of the SMYD2 promoter could be a causal factor of decreased SMYD2 expression, which has previously been implicated in adverse cardiovascular physiology and increased inflammation.
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Hemmler, André [Verfasser]. "In-Silico Endovascular Repair of Abdominal Aortic Aneurysms / André Hemmler." München : Verlag Dr. Hut, 2020. http://d-nb.info/1219471364/34.
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Krenzien, Felix, Ivan Matia, Georg Wiltberger, Hans-Michael Hau, Moritz Schmelzle, Sven Jonas, Udo X. Kaisers, and Peter T. Fellmer. "Early prediction of survival after open surgical repair of ruptured abdominal aortic aneurysms." Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-156960.
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Background: Scoring models are widely established in the intensive care unit (ICU). However, the importance in patients with ruptured abdominal aortic aneurysm (RAAA) remains unclear. Our aim was to analyze scoring systems as predictors of survival in patients undergoing open surgical repair (OSR) for RAAA. Methods: This is a retrospective study in critically ill patients in a surgical ICU at a university hospital. Sixty-eight patients with RAAA were treated between February 2005 and June 2013. Serial measurements of Sequential Organ Failure Assessment score (SOFA), Simplified Acute Physiology Score II (SAPS II) and Simplified Therapeutic Intervention
Scoring System-28 (TISS-28) were evaluated with respect to in-hospital mortality. Eleven patients had to be excluded from this study because 6 underwent endovascular repair and 5 died before they could be admitted to the ICU. Results: All patients underwent OSR. The initial, highest, and mean of SOFA and SAPS II scores correlated significant
with in-hospital mortality. In contrast, TISS-28 was inferior and showed a smaller area under the receiver operating curve. The cut-off point for SOFA showed the best performance in terms of sensitivity and specificity. An initial SOFA score below 9 predicted an in-hospital mortality of 16.2% (95% CI, 4.3–28.1) and a score above 9 predicted an
in-hospital mortality of 73.7% (95% CI, 53.8–93.5, p < 0.01). Trend analysis showed the largest effect on SAPS II. When the score increased or was unchanged within the first 48 h (score >45), the in-hospital mortality rate was 85.7% (95% CI, 67.4–100, p < 0.01) versus 31.6% (95% CI, 10.7–52.5, p = 0.01) when it decreased. On multiple regression analysis, only the mean of the SOFA score showed a significant predictive capacity with regards to mortality (odds ratio
1.77; 95% CI, 1.19–2.64; p < 0.01). Conclusion: SOFA and SAPS II scores were able to predict in-hospital mortality in RAAA within 48 h after OSR. According to cut-off points, an increase or decrease in SOFA and SAPS II scores improved sensitivity and specificity.
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Hua, Fang. "Role of angiotensin II and inflammatory cells in the development of human abdominal aortic aneurysm /." [St. Lucia, Qld.], 2004. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18409.pdf.
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Griffin, Kathryn Jane. "The role of transglutaminases in the development of abdominal aortic aneurysms." Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/13774/.
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Abdominal aortic aneurysms (AAA) are dilatations of the abdominal aorta that are prone to rupture with fatal consequences. AAAs (diameter >3cm) are present in ~4% of men aged >65years. AAA formation is initiated with the loss of medial elastin. Responses to this include synthesis of tropoelastin and deposition of collagen. Dilatation occurs following degradation of this collagen, secondary to release and activation of matrix metalloproteinases (MMPs) by invading macrophages. Elastin is strengthened and protected from proteolysis by cross-linking. Transglutaminases (TGs) introduce cross-links between protein chains and have been implicated in arterial repair; TG2 has been shown to be induced early in experimental aneurysm development. The literature suggests that TG2 and the homologous enzyme FXIII-A may act cooperatively or may compensate for each other in the face of deficiency. We have bred TG2-/-, FXIII-A-/- and TG2-/-.FXIII-A-/- double knockout (DKO) mice to characterise their basal vessel structure and function and investigate their susceptibility to aneurysm formation. This work has shown that both FXIII-A and TG2 are involved in the maintenance of basal vessel integrity and that aortic permeability is increased in mice lacking FXIII-A. In the absence of the repair function of TG2, the DKO mice develop extensive cardiovascular fibrosis and exhibit decreased vessel tension. We have not seen evidence of a clear protective effect of TG2, however our DKO animals showed an (unexpected) decreased propensity to aneurysm formation. In an extended model there is evidence that aneurysm initiation and progression occur by different mechanisms and that TG2 plays a role in prevention of the latter. This thesis has also shown that TG2 and/or FXIII-A are not essential for vascular calcification. The results presented here help to define the common and distinct functions of FXIII-A and TG2 in arterial structure and function, and provide evidence in their evaluation as potential therapeutic targets.
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Wener, Evan. "The biomechanics of ascending aortic aneurysms: The effect of measurement technique." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=117062.
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An ascending aortic aneurysm is a pathologic enlargement of the ascending portion of the aorta. Comorbidities of dilation include aortic valve disease and connective tissue disorders. If the ascending aorta exceeds a threshold diameter, open heart surgery is recommended. This is a traumatic procedure and the recovery is demanding. As our population ages and with improved technologies to diagnose the disease, the number of cases will increase every year. Understanding the mechanics of ascending aortic tissue will help cardiac surgeons make timely decisions on when to intervene. There are many ways to characterize the mechanical properties of aortic tissue. In this study, we used biaxial and uniaxial tensile testing with an optical tracking system to record the Green-Lagrangian (Green strain) strain. Engineering and true stiffness values were calculated and compared along with patient characteristics. Aortas were classified by valve type as healthy, tricuspid, bicuspid type 1 and bicuspid type 2. The results show that diseased tissue does behave differently than healthy tissue indicating that a local remodeling does occurs to the aortic wall. There are also differences in the mechanics between the types of diseased valves suggesting that valve type also affects the way the aortic wall responds to the disturbed hemodynamic environment. Correlations between stiffness and patient characteristics show that no matter which experimented technique or method of stiffness calculation is used, relationships are generally conserved. The only difference is the magnitude of the elastic modulus. The conclusions drawn from the data would not change whether biaxial or uniaxial experiments were performed. However when comparing engineering and true stiffness, only 7/12 covariances were similar and therefore the conclusions are inconsistent.Un anévrisme de l'aorte ascendante est un agrandissement pathologique de l'aorte ascendante. Les comorbidités de dilatation incluent les maladies de la valve aortique et du tissu conjonctif. Si l'aorte ascendante dépasse un diamètre seuil, la chirurgie à cœur ouvert est recommandée. Il s'agit d'une procédure traumatique et la récupération est exigeante. Comme notre population vieillit et que les technologies pour diagnostiquer la maladie se sont beaucoup améliorées, le nombre de cas décelé va augmenter chaque année. Comprendre les mécanismes du tissu aortique ascendant aidera les chirurgiens cardiaques à prendre les bonnes décisions au bon moment. Il y a plusieurs façons de caractériser les propriétés mécaniques du tissu aortique. Dans cette étude, nous avons utilisé les essais de traction biaxiale et uniaxiale avec un système de suivi optique pour enregistrer la souche Green-Lagrange (souche verte). Valeurs de rigidité d'ingénierie et de vrai ont été calculées et comparées avec les caractéristiques des patients. Les aortes ont été classées en 4 types de valves : bonne santé, tricuspides, bicuspides de type 1 et bicuspides de type 2. Les résultats montrent que les tissus malades sont différents des tissus en bonne santé qui indiquent qu'un remodelage local se produit sur la paroi aortique. Il existe aussi des différences dans le mécanisme des différents types de valvules qui suggèrent que le type de valve affecte également la façon dont la paroi aortique répond à l'environnement perturbé hémodynamique. Les corrélations entre les caractéristiques de rigidité et le patient nous montrent que quelque-soit la technique ou la méthode de calcul utilisée pour la rigidité, les relations sont généralement conservées. La seule différence est la grandeur du module d'élasticité. Les conclusions tirées de ces données ne changeraient pas, peu importe le type d'expérimentation effectué; biaxiale ou uniaxiale. Cependant, lorsque l'on compare la rigidité d'ingénierie et de vrai, seulement 7 covariances sur 12 sont similaires et les conclusions sont contradictoires.
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Maier, Andreas [Verfasser]. "Computational Modeling of Rupture Risk in Abdominal Aortic Aneurysms / Andreas Maier." München : Verlag Dr. Hut, 2013. http://d-nb.info/103728707X/34.
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Fraser, Katharine H. "Computational estimation of haemodynamics and tissue stresses in abdominal aortic aneurysms." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/24588.
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Abdominal aortic aneurysm is a vascular disease involving a focal dilation of the aorta. The exact cause is unknown but possibilities include infection and weakening of the connective tissue. Risk factors include a history of atherosclerosis, current smoking and a close relative with the disease. Although abdominal aortic aneurysm can affect anyone, it is most often seen in older men, and may be present in up to 5.9% of the population aged 80 years. Biomechanical factors such as tissue stresses and shear stresses have been shown to play a part in aneurysm progression, although the specific mechanisms are still to be determined. The growth rate of the abdominal aortic aneurysm has been found to correlate with the peak stress in the aneurysm wall and the blood flow is thought to influence disease development. In order to resolve the connections between biology and biomechanics, accurate estimations of the forces involved are required. The first part of this thesis assesses the use of computational fluid dynamics for modelling haemodynamics in abdominal aortic aneurysms. Boundary conditions from the literature on healthy patients are used, along with patient specific aneurysm geometries, to obtain a first estimate of blood flow patterns and haemodynamic wall parameters within the aneurysms. The use of healthy patient boundary conditions is difficult to justify as the presence of the aneurysm is likely to alter the flow rate in the aorta. This is investigated with a Doppler ultrasound study of blood velocities in the normal and aneurysmal aorta. Archetypal waveforms reveal a significant difference in the diastolic maximum of young healthy volunteers and AAA patients. The archetypal aortic velocity wave for patients with abdominal aortic aneurysm is used to calculate the haemodynamics in a group of patients and these calculations are compared with those obtained using patient specific boundary conditions, and with phase-contrast magnetic resonance imaging measurements of blood velocity. With the correct z-velocity profile at the entrance to a short inlet section proximal to the aneurysm, the calculated velocities agreed qualitatively with the measured velocities. However, the velocities calculated using the correct inlet flow rate, but a simple velocity profile, are quite different from the measurements. These results show that the correct velocity profile at the aneurysm entrance is required to predict velocities within the aneurysm cavity. In reality the blood and the artery wall interact: the blood flow domain continually dilates and contracts, altering the flow patterns; the flow controls the pressure on the wall and therefore the stresses within it. The influence of this fluid-structure interaction on the blood flow and tissue stresses is investigated in axially symmetric models of abdominal aortic aneurysm. Modelling of the complete fluid-structure interaction reveals how the pressure and flow waves are distorted by the aneurysm geometry. This distortion, which is absent from both static pressure and one way coupled models, accounts for the small errors in tissue and wall shear stresses obtained when using these models with lower computational complexity. These errors vary with the type of modelling as well as the aneurysm diameter and elasticity. A one dimensional, lumped parameter model of the aneurysm is developed to elucidate the effect of aneurysm geometry on the propagation of pressure and flow waves. It reveals interesting consequences of the diameter of the aneurysm on its inductance and resistance, and its use in improving the outlet pressure boundary condition is investigated.
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Kotze, C. W. "In vivo quantification of metabolic activity in aortic aneurysms using PET." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1463147/.
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Objective: To investigate the role of hybrid 18F-FDG PET/CT as a potential risk-stratification tool of aneurysm expansion by measuring metabolic activity on PET and textural analysis on CT in abdominal aortic aneurysm (AAA). Histological markers of AAA wall inflammatory cell infiltrate and enzymatic degradation have been associated with increased 18F-Fluorodeoxyglucose (18F-FDG)-Positron Emission Tomography /Computed Tomography (PET/CT) uptake. Methods: Fifty patients with asymptomatic infrarenal AAA enrolled under surveillance at one of our institutions underwent 18F-FDG-PET/CT. Seventeen subjects were investigated for increased glucolysis in the AAA wall and optimal circulation imaging time for 18F-FDG. In 25 subjects the relationship between aneurysm metabolic activity and expansion was explored. Forty subjects had AAA CT textural analysis (CTTA) parameters performed on the CT component of PET/CT and were studied in relation to aneurysm expansion. Twenty-four subjects had circulating biomarkers analysed. Whole vessel assessment, region of interest analysis and the role of correcting for background blood pool activity were explored. Results: Thirteen of seventeen subjects investigated for increased 18F-FDG uptake had an AAA wall SUVmax > 2.5. In 17 subjects assessed for optimal circulation imaging time for 18F-FDG, no significant advantage in imaging at 3h over 1h after 18F-FDG injection was observed. 18F-FDG uptake correlated inversely with future AAA expansion in the preliminary group of 25 patients and in 40 subjects who also had CTTA. In subjects who had CTTA, coarse texture showed an inverse association with 18F-FDG uptake and medium coarse texture correlated with future AAA expansion. In 24 AAA patients who had serum biomarker assays, significantly higher levels of high sensitivity matrix metalloproteinase-9 (hsMMP-9) and hsMMP-2 compared to healthy controls were found. There was no correlation between AAA 18F-FDG uptake and levels of hsMMP-9, hsMMP-2, hs-interferon-γ and hs-C-reactive protein. Conclusions: In-vivo 18F-FDG PET/CT data indicated that small AAA show increased glucose metabolism. Relationships between AAA 18F-FDG uptake, CTTA and future expansion were identified. AAA18F-FDG PET/CT shows potential to identify subjects at risk of significant expansion. AAA metabolism may not relate to serum levels of certain inflammatory biomarkers.
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Sandford, Rebecca M. "The role of the CCR5 Δ32 polymorphism in abdominal aortic aneurysms." Thesis, University of Leicester, 2008. http://hdl.handle.net/2381/29904.
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C-C Chemokine receptor 5 (CCR5) is involved in the regulation of the inflammatory response. Abdominal aortic aneurysms (AAA) may arise as the result of a chronic inflammatory process which is influenced by genetic predisposition. The CCR5 gene is associated with a 32 base pair deletion (the Δ32 polymorphism). The aim of this study was to investigate the role of the CCR5 Δ32 polymorphism in the development of AAA. A case control study was conducted including 285 patients with AAA and 273 control subjects. A blood sample was taken from each individual and DNA extracted. CCR5 genotype was determined using the polymerase chain reaction (PCR). Flow cytometry was used to investigate the biological activity of the Δ32 polymorphism. There was no significant difference between the AAA and the control group in relation to the Δ32 allele frequency (AAA group10%, control group=12%, P=0.82, chi squared analysis). Genotype analysis revealed no significant difference between the groups (AAA vs controls, wild type homozygotes=82% vs 77% heterozygotes=16% vs 21%, vs Δ32 homozygotes= 2% and 2% respectively, P=33, chi squared analysis). The polymorphism was shown to be biologically active with the number of Δ32 alleles correlating with cell expression of CCR5 as detected with flow cytometry (P = < 0.05). This study demonstrates that the CCR5 Δ32 is a biologically active genetic polymorphism, however, there is no association between this polymorphism and AAA.
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Crawford, Kevin John. "THE ROLE OF CAVEOLAE IN THE FORMATION OF ABDOMINAL AORTIC ANEURYSMS." Diss., Temple University Libraries, 2015. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/312992.
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Cell BiologyPh.D.
Abdominal aortic aneurysm (AAA) is a major cardiovascular disease and involves enhancement of renin-angiotensin system and recruitment/activation of inflammatory factors such as matrix metalloproteases (MMP's). Caveolae has been shown to play a role in a number of different cardiovascular diseases through different mechanisms including regulation of oxidative stress, inflammation and degradation of extracellular matrix components through MMP's. In addition, endothelial cell caveolae are known to localize the Ang-II (AT1) receptor and regulate renin-angiotensin signaling. Based on these findings, we evaluated the role of caveolae in AAA formation in the murine model. Here, eight week old mice were co-infused with Ang-II and BAPN, a lysyl oxidase inhibitor, to induce AAA. We found that mice lacking the main structural protein of caveolae, caveolin-1, did not develop AAA compared to WT animals in spite of hypertensive blood pressures measured by telemetry in both groups. This finding suggests that intact Ang-II signaling remains in place in caveolin-1 knockout mice. To begin to address the underlying mechanism by which caveolae contributes to AAA, we measured the level of oxidative stress and MMP's in aneurysms. We found an increased expression of MMP-2 and MMP-9 in vessels of WT mice displaying aneurysms. This increase in expression was not observed in Cav-1 knockout mice. Furthermore, KO mice showed less oxidative stress then their WT counterparts as assessed by anti-nitrotyrosine staining. Next we examined the characteristics of early AAA formation in wild-type mice. We found caveolae associated proteins, endothelial nitric oxide synthase (eNOS) and NADPH oxidase 2 (Nox2), were upregulated in early AAA formation, particularly in the endothelium. Also, Vascular Cell Adhesion Molecule (VCAM) was upregulated in the endothelium. However, macrophage infiltration and MMP-2 activation was not observed in early AAA development. In order to elucidate the role of endothelial caveolae in the formation of AAA, we induced AAA, as previously described, in endothelial specific cav-1 knockout mice. Preliminarily findings show endothelial specific knockout mice do not form AAA as compared to their WT littermates. In conclusion, caveolae appears to play a critical role in the formation of AAA in mice via oxidative stress, and recruitment and/or activation of MMPs, specifically MMP-2 and MMP-9. Early markers of AAA formation include VCAM, NOX2, eNOS, and protein nitration. Also, preliminary results indicate that endothelial specific knockout mice do not develop AAA.
Temple University--Theses
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Chun, Young Jae. "Thin film NiTi endovascular stent grafts for cerebral and aortic aneurysms." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1835100701&sid=7&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Malecki, Cassandra. "Modulators of phenotypic variation associated with genetically triggered thoracic aortic aneurysms." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/27298.
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Genetically triggered thoracic aortic aneurysms (TAA) are potentially life threatening, with timely intervention essential to the survival of patients. The phenotypic presentation of TAA’s is highly variable between patients, suggesting a substantial complexity associated with the pathogenesis of this disease. This has led to an extensive search for phenotype-genotype correlations between the nature of the causative mutation and the severity of disease. However, there has been limited success, emphasising the need for investigation of genetic modifiers lying outside the causative gene. This thesis aimed to investigate the potential relationship between disease modifiers and phenotypic modulation in TAA development, focusing on three potential modifiers: genetic, epigenetic and post-transcriptional.
The role of single nucleotide polymorphisms (SNPs) as genetic modifiers of disease severity in genetically triggered TAA was assessed through genotyping SNPs in candidate genes associated with TAA pathogenesis; specifically, matrix metalloproteinases (MMPs), in an MFS cohort. SNP genotypes in MMP-2, 3 and 9 showed a correlation with cardiovascular (CV) clinical parameters including aortic diameter, Z-score and ejection fraction, indicating the ability of SNP genotypes to modulate severity of CV manifestations in MFS.
Epigenetic mechanisms have been implicated in numerous diseases, with DNA methylation being one of the most well studied epigenetic markers. Investigation of the DNA methylation profile in MFS when compared to controls showed differential methylation of genes involved in the regulation of inflammatory pathways and cardiac contraction. Correlations between DNA methylation and severity of cardiovascular complications in MFS demonstrated that DNA methylation of IL-17RA was significantly higher in patients with a more severe disease phenotype, further implicating the inflammatory response in MFS-TAA progression. Complimentary to these results, DNA methylation of redox related genes (PON2, PON3, CYP1A1, FLJ44606 and TP53INP1) correlated with CV parameters.
RNA binding proteins (RBPs) have emerged as being important proteins in posttranscriptional gene regulation, with an increase in the number of CGG trinucleotide repeats in the fragile X mental retardation gene (FMR1) causing Fragile X syndrome; a predominately neurological disorder that also presents with connective tissue abnormalities similar to those is MFS, including aortic dilation. For the first time, this study has shown the presence of FMRP, the protein product of FMR1, in human aortic tissue, with endothelial cells and VSMC’s shown to express the protein, providing preliminary evidence to support further mechanistic investigations of how dysregulation of FMRP may give rise to an aneurysmal phenotype. Additionally, FMRP may be a possible modifier of phenotypic presentation in MFS, although a pilot study in this thesis did not demonstrate a relationship.
This research demonstrates that the phenotypic variability seen in MFS can be modulated by several mechanisms. Continuing to understand markers indicative of a predisposition to the development of severe disease will ultimately allow for more accurate prognostication and timely surgical intervention and will assist in defining novel therapeutic targets.
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Bridge, Katherine Isabella. "The role of thrombin activatable fibrinolysis inhibitor in abdominal aortic aneurysms." Thesis, University of Leeds, 2015. http://etheses.whiterose.ac.uk/10749/.
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Thrombin-activatable fibrinolysis inhibitor (TAFI) prevents the breakdown of fibrin clots through its action as an indirect inhibitor of plasmin. Patients with abdominal aortic aneurysms (AAA), in common with a number of cardiovascular diseases, display an altered fibrin clot structure, with denser clots that have smaller pores and an increased resistance to lysis. Murine studies have implicated a potential role for TAFI in AAA disease. This study aimed to investigate the role of TAFI in human AAA, and to complement this with an investigation into the effect of TAFI inhibition on AAA development and progression in-vivo. By measuring the plasma levels of TAFI zymogen, activated and inactivated TAFI, and the TAFI activation peptide in plasma samples, and using clot lysis assays to determine in-vitro TAFI activity, this study indicated increased turnover of TAFI in patients with AAA. Further to this, it was determined that the delay in lysis previously demonstrated in patients with AAA could be corrected through the inhibition of TAFI. Inhibition of TAFI in-vivo resulted in a decrease in mortality in the Angiotensin II model of AAA. The site of action of the inhibitor determined the effect on AAA formation, however, with inhibition of plasmin-mediated TAFI activation resulting in a decrease in AAA formation rates, whilst inhibition of all active TAFI resulted in an increase in AAA formation rates. Delayed TAFI inhibition following the formation of AAA had no effect on AAA progression. This study demonstrated evidence of increased TAFI turnover in patients with AAA, whilst in-vivo studies indicate a role for TAFI early in the development of AAA disease.
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Maroney, Roy Thomas. "Missed opportunities for the detection of abdominal aortic aneurysms : a retrospective study of eighteen patients presenting with a ruptured or acute symptomatic abdominal aortic aneurysm." Master's thesis, University of Cape Town, 1997. http://hdl.handle.net/11427/25566.
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A ruptured abdominal aortic aneurysm (AAA) has a mortality of 80 percent. The majority of these cases present as medical emergencies, with 50 percent dying before they reach hospital. Twenty percent are not operated on because of an incorrect diagnosis and of the surviving 30 percent, there will be a peri-operative mortality of 40 percent. Thus only 20 percent of patients survive this condition. It is important to state that the long-term survival reported for patients undergoing AAA surgery approximates that of age-matched populations. This is in contrast to patients undergoing a coronary bypass procedure, where the long-term survival is affected by factors such as hypertension, angina and peripheral vascular disease. If the condition is diagnosed electively, the mortality rate is reduced to less than 5 percent. The researcher obtained the records of 18 patients who had presented to the vascular service at the New Kingsbury Hospital with a diagnosis of a ruptured or acute symptomatic AAA. He interviewed the referring family doctor and also obtained information from the case records to determine whether there were missed opportunities for the detection of such aneurysms. The results of the research showed that 12 general practitioners (GP's) out of a group of 13, were unaware that abdominal ultrasound is a highly specific and sensitive method for detecting AAA's. Only one of the group of 13 GP's regularly screens for AAA. The diagnosis of AAA was missed in 12 of the 18 patients. In this series the mean diameter of the aorta was 7,67 cm which is considered to be easily palpable. Five of the patients were referred to specialists for incidental reasons and they all failed to detect the AAA. The majority of patients with AAA's have at least 2 associated risk factors. The patients consulted their GP at least 5 times over the 24 month period. The GP's are not aware of the different modes of presentation, associated risk factors nor the value of screening for AAA's. Ten of the group of 13 GP's profess to engage in some form of Continuing Medical Education (CME). I have suggested a few guidelines to encourage family physicians to screen for AAA in all males over the age of 60, especially if they have risk factors, such as hypertension, a current or former cigarette smoker, coronary artery disease, peripheral vascular disease and a family history of AAA. The examination should include a thorough abdominal palpation and referral for an abdominal ultrasound examination to obtain the precise diameter of the AAA as treatment depends on the size of the AAA.
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Wang, Shuo. "Development of a novel uncovered stent system for the management of complex aortic aneurysms." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/288381.
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Endovascular aortic repair (EVAR) is a minimally invasive alternative to open surgery for the treatment of aortic aneurysms (AA). However, standard EVAR is not applicable to complex AA with involvement of vital branches, which could be occluded by the endograft. As an emerging technique, the concept of multiple overlapping uncovered stents (MOUS) have been proposed to manage complex lesions. MOUS was used to modulate the flow pattern inside the aneurysm sac, and promote the thrombus formation followed by the aneurysm shrinkage. In this dissertation, we sought to investigate the mechanism of MOUS-induced flow modulation and key factors associated with the success of this novel technique: - The mechanical behaviour of AA was characterised by uniaxial material tests (Chapter 4). A Bayesian framework was proposed for material constants identification. They were found correlated to the microstructure of tissue fibre network and were capable in differentiating tissue types. - Solid-to-solid interaction and one-way fluid-solid interaction (FSI) analysis was performed based on patient-specific computer tomography angiography (Chapters 5&6). Structural stress concentrations were observed within the landing zones, which increased with the number of stents deployed. In the parameter studies (Chapter 6), the overall porosity was identified as the dominant factor of the flow-diverting outcome, while cross-stent structures of MOUS had limited influence. - The pathological effect of structural stress concentration induced by an implanted device was further studied in rabbit models (Chapter 7). The wall structural stress and fluid shear stress were obtained from FSI analysis based on magnetic resonance imaging (MRI), and correlated to plaque characteristics. Both high structural stress and low fluid shear stress were found correlated to plaque initialisation and increased inflammation. Overall, MOUS modulates the blood flow with robust performance under different overlapping patterns. Image-based biomechanical analysis can optimise MOUS design and can contribute to personalised pre-surgery planning.
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Stenson, Katherine Mary. "The use of endovascular sealing for the treatment of abdominal aortic aneurysms." Thesis, St George's, University of London, 2017. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.719393.
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Endovascular aneurysm sealing (EVAS) offers a novel approach to the treatment of abdominal aortic aneurysm (AAA). Since the commercialisation of the device early in 2013. it has been used to treat infrarenal AAA. More recently, it has been used in combination with chimney grafts (Ch-EVAS) to treat supra- and juxtarenal aneurysms. As a new paradigm in endovascular aortic treatment, very little is known about the effect of EVAS on the incidence of post-implantation syndrome (PIS) and its potential ramifications. There is also no standardised protocol for assessing the three-dimensional aortic morphology before or after the EVAS procedure. This work will address these four areas. 1.2 Methods The clinical outcomes sections will involve retrospective analysis of prospectively collected data on patients undergoing the EVAS procedure and its applications. These data will include pre-, intra-, peri- and postoperative details. PIS will be assessed by evaluating the pre- and postoperative information from two groups of patients who underwent AAA repair with EVAS or EVAR. This will allow comparisons to be made regarding the incidence of PIS. Measurement protocols will be applied to pre- and post-EVAS CT scans by a set of trained observers to detect intra- and interobserver variability and to determine the accuracy and reproducibility of the protocols. 1-3 Results The results from the infrarenal EVAS study show a very high rate of technical success with low rates of unresolved endoleak, but with a worrying incidence of secondary rupture. Fewer adverse events are seen in cases where the instructions for use are adhered to. The results from the Ch-EVAS study show a very high level of technical success with low complication rates and a low stroke rate. In the PIS study, results showed that the incidence was significantly lower following EVAS when compared with EVAR. The measurement protocols yielded results that demonstrated generally low variation between observers. 1.4 Conclusion EVAS is a successful addition to the range of treatments already available for AAA. As with all endovascular treatments, it is most successful when used with the instructions for use. Its use with chimney grafts fills a particular therapeutic gap. Incidence of PIS is significantly decreased when compared with that after EVAR and this is associated with significantly shorter hospital stays. The measurement protocols allow accurate assessment of morphology and will be valuable in determining preoperative suitability for treatment and assessing postoperative performance.
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Altuwaijri, Omar. "Advanced computer modeling of abdominal aortic aneurysms to predict risk of rupture." Thesis, University of Hull, 2012. http://hydra.hull.ac.uk/resources/hull:6905.
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An abdominal aortic aneurysm (AAA) is an abnormal enlargement of the aorta which is related to weakness of the vessel wall (associated with degradation of connective tissue), and if left untreated will lead to rupture and cause death in 78% to 94% of cases. Approximately 7,000 deaths each year in the United Kingdom are caused by AAA rupture. AAA repair requires surgical intervention but the surgery itself has a mortality rate of about 5% in patients with stable AAA. The decision to undertake the surgery is made depending on the aortic maximum diameter of ≥5 cm. However, it is observed that rupture sometimes occurs in aneurysms with smaller diameter, thereby creating the need for better criteria for surgical intervention. Therefore, (biomechanical) indicators of AAA rupture were introduced as a superior criterion to the maximum diameter for predicting the risk AAA rupture. Several studies that have been conducted on abdominal aortic aneurysms have suggested that peak wall stress may be a more reliable predictor of the risk of AAA rupture. This thesis is a continuation of a previous study undertaken at the University of Hull which investigated a number of biomechanical factors that affect the AAA wall stress magnitude and distribution. Novel results were gained which may help in the understanding of AAA growth and rupture events. For the first time, it is proposed that aspect ratio has an effect on the stress magnitude, location and distribution of the outer wall of AAA. These findings were used to introduce an empirical relationship between the aneurysm aspect ratio and maximum wall stress. This empirical relationship could be used as an additional clinical indicator to predict the location and magnitude of maximum wall stress where a rupture may develop. Analysis of the porosity of the thrombus was introduced for the first time in this work using the simulation of mass transport of blood flow in an AAA, showing novel results for the possible role of blood flow on the site of growth and rupture for AAA. Furthermore, the results of this research may also explain the conflicting views on aneurysm shape and the role of the thrombus as previously reported in the literature. The work carried out in this research used simplified AAA geometries to allow the isolation of specific aneurysm parameters. Clearly, the next stage would include the application of the ideas and results developed here to more complex patient-specific geometries.
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Al-Barjas, Hamad Saud. "Haemostatic risk factor clustering in the pathogenesis of abdominal aortic aneurysms (AAA)." Thesis, University of Leeds, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494596.
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Bevis, Paul Michael. "Abdominal aortic aneurysms and the association with a systemic connective tissue disorder." Thesis, University of Bristol, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.544428.
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Chong, Chuh Khiun. "Endovascular stent-graft repair of abdominal aortic aneurysms : an in vitro modelling." Thesis, University of Liverpool, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367821.
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IBRAHIM, LUCAS BOABAID. "NUMERICAL AND EXPERIMENTAL ANALYSIS OF MECHANICS OF FORMATION OF ABDOMINAL AORTIC ANEURYSMS." PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2010. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=16813@1.
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COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOREsta tese tem por objetivo investigar numérica e experimentalmente a mecânica da formação dos aneurismas na aorta abdominal. A parte experimental foi realizada no Laboratório de Membranas e Biomembranas utilizando-se tubos de silicone com a geometria aproximada da aorta sob pressão hidrostática. Foi investigada a pressão necessária à formação dos aneurismas e o comportamento do material ensaiado. A parte numérica foi realizada por meio do método dos elementos finitos através do programa ABAQUS (6.8.1). Com a análise numérica foi validada a análise experimental. Foram estudados casos de imperfeição geométrica e física do material, usando equações constitutivas propostas para o material da aorta.
The aim of this work is to investigate numerically and experimentally the mechanics of aortic aneurisms. The experimental part was performed at the Laboratory of Membranes and Biomembranes using silicone tubes with the geometry of the aorta under hydrostatic pressure. We investigate the behavior of the material tested and the critical pressure, this is the pressure necessary for the formation of aneurysms. The numerical analysis is done using the finite element code ABAQUS (6.8.1), and is validated by the experimental analysis. Some studies of geometrical and physical imperfections are performed, as well as the ones with constitutive equations for the material of the aorta.
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Ehsan, Saima. "An investigation into the plasma protein profile of Abdominal Aortic Aneurysms (AAA)." Thesis, University of Leicester, 2013. http://hdl.handle.net/2381/38549.
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Dattani, Nikesh. "The significance of glucose transporters in the pathogenesis of abdominal aortic aneurysms." Thesis, University of Leicester, 2018. http://hdl.handle.net/2381/42531.
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Abdominal aortic aneurysm (AAA) is associated with significant mortality worldwide. At present, the only treatment involves an operation. Understanding the pathogenesis is important to help develop new drug therapies aimed at slowing aneurysm growth. Diabetes mellitus (DM) has been shown to be negatively associated with AAA however the mechanisms underlying this relationship are poorly understood. This thesis first confirmed the robustness of this epidemiological relationship through a meta-analysis of >70 studies and then, using whole aortic tissue samples (WATS) and aortic smooth muscle cells (AoSMCs) from patients with and without AAA, examined the importance of glucose transporters (GLUTs), a group of proteins responsible for sugar transport across cell membranes, in the pathogenesis of AAA and in explaining the negative relationship between DM and AAA. Comparing WATS from patients with and without AAA, gene expression of GLUT3 (p=0.004) and GLUT6 (p=0.04) and protein expression of GLUT1 (p=0.002), GLUT3 (p=0.002) and GLUT6 (p=0.004) were significantly higher in WATS from AAA patients. Comparing AoSMCs from patients with and without AAA, gene expression of GLUTs was similar between groups however GLUT activity was significantly higher in AoSMCs from patients with AAA (p=0.02). To study the effect of DM on GLUTs, AoSMCs from patients with and without AAA were exposed to increasing levels of hyperglycaemia (4.6mmol/L - 50mmol/L). Hyperglycaemia was not associated with a significant change in the gene expression of GLUTs, cathepsins or TIMPs, however hyperglycaemia within the physiological range (up to 25mmol/L) was associated with a significant decrease in GLUT activity (p=0.01) selectively in the AoSMCs from AAA patients, independent of any hyperosmolar effect. In conclusion, these results suggest that glucose transporters are important in the pathogenesis of AAA and may be involved in regulating the protective effect of DM on AAA. Targeting glucose transporters to slow aneurysm growth merits further investigation.
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Javadzadegan, Ashkan. "Computational fluid dynamics modelling of atherosclerotic coronary arteries and abdominal aortic aneurysms." Thesis, The University of Sydney, 2014. http://hdl.handle.net/2123/11735.
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This thesis aimed to use three-dimensional quantitative coronary angiography (3D-QCA), computational fluid dynamics (CFD), fluid-structure interaction (FSI) and particle image velocimetry (PIV) techniques in idealised and realistic coronary artery models based on data from patients in order to investigate the relation between haemodynamic forces and lesion morphology. The first aim was to assess the effect of lesion severity and eccentricity on important haemodynamic factors including flow recirculation and shear stress using CFD and PIV. The results showed that the extent of flow recirculation is much more sensitive to mild changes in the severity of intermediate stenoses than is peak shear. The second aim was to find the correlation between fractional flow reserve (FFR), a gold standard to measure the functional significance of coronary stenoses, lesion eccentricity and vessel distensibility using 3D-QCA and FSI methods. The results demonstrated that the coronary arteries with similar lesion morphology but different vessel distensibility are likely to experience different FFR. The third aim was to explore the impact of degree of freedom of coronary arteries on important haemodynamic factors. The results showed that modelling of coronary arteries as rigid vessels could result in treating a non-significant lesion as significant because the rigidity assumption overestimates the amount of flow abnormalities in coronary arteries. Overall, the greater the degree of freedom of movement, the lower the maximum wall shear stress (WSS) and the smaller the area of low WSS. Last but not least, the effect of spiral flow on haemodynamic parameters in an elastic model of abdominal aortic aneurysm (AAA) was investigated. The results demonstrated that neglecting the spiral effects of flow in the modelling of AAAs can result in overestimation of wall stress and the artery wall expansion rate.
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López-Linares, Karen. "Image analysis and deep learning to support endovascular repair of abdominal aortic aneurysms." Doctoral thesis, Universitat Pompeu Fabra, 2019. http://hdl.handle.net/10803/667102.
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An abdominal aortic aneurysm (AAA) is a focal dilation of the aorta that may lead to its rupture. The most common treatment for AAAs is endovascular aneurysm repair (EVAR). EVAR implies lifelong postoperative surveillance using Computed Tomography Angiography (CTA), due to the potential appearance of complications. This thesis sets the basis for intelligent CTA image analysis to support post-operative follow-up of AAAs, providing clinicians with valuable information to prognose the behavior of the aneurysm.
First, novel pre-operative and post-operative AAA segmentation approaches are developed, based on Convolutional Neural Networks (CNN). Initially, 2D AAA detection and segmentation CNNs are proposed. Then, segmentation is extended to 3D to increase segmentation accuracy. Precise AAA segmentation is the basis for a good AAA follow-up. It allows to measure aneurysm volume, which is thought to be a better indicator for
aneurysm rupture than the current AAA diameter measurements. Furthermore, it enables more complex analyses of AAA morphology and deformations.
Subsequently, a methodology for post-operative CTA time-series registration and aneurysm biomechanical strain analysis is also proposed. From these strains, quantitative image-based descriptors are extracted and correlated with the long-term patient prognosis. The extracted descriptors are the basis for possible future imaging biomarkers to be used in clinical practice to assess patient prognosis and to enable informed decision making after EVAR.
Finally, the technological developments in the thesis are applied to solve complex segmentation problems in other clinical domains, such as pectoral muscle segmentation from mammograms and pulmonary artery segmentation from CT scans.
Validation of the 3D AAA segmentation approach proposed in this thesis is being carried out with the aim of integrating it in a commercial product.El aneurisma de aorta abdominal (AAA) es una dilatación focal de la aorta que puede provocar su ruptura. El tratamiento habitual es la reparación endovascular (EVAR), que conlleva un seguimiento postoperatorio de por vida en base a imágenes de angiografía por tomografía computarizada (CTA) para detectar posibles complicaciones. Esta tesis establece la base para el análisis inteligente de imágenes CTA para apoyar el seguimiento postoperatorio de los AAA, proporcionando a los profesionales médicos información valiosa para predecir el comportamiento del aneurisma. Primero, se han desarrollado algoritmos de segmentación de AAA a partir de CTA preoperatorias y postoperatorias, basados en redes neuronales convolucionales (CNN). Inicialmente, se han propuesto CNNs 2D para la detección y la segmentación de AAAs. Posteriormente, el algoritmo de segmentación se ha extendido a 3D para mejorar su precisión, ya que ésta es la base para un buen seguimiento. Permite medir el volumen del aneurisma, que se considera un mejor indicador de riesgo de ruptura del AAA que la aproximación actual en base a su diámetro. Además, permite realizar análisis más complejos de la morfología y las deformaciones del AAA. Una vez obtenida la segmentación, se ha propuesto una metodología para el registro de series de CTA postoperatorias y el subsiguiente análisis biomecánico de las deformaciones del aneurisma. Dichas deformaciones se han cuantificado mediante descriptores de imagen y se han correlacionado con el pronóstico del paciente a largo plazo. Los descriptores extraídos establecen la base para el desarrollo de futuros biomarcadores de imagen que puedan ser utilizados en la práctica clínica para evaluar el pronóstico del paciente y para dar soporte al médico en sus decisiones tras una intervención EVAR. Por último, la experiencia adquirida en la tesis ha permitido aplicar algunas de las tecnologías para la resolución de problemas de segmentación complejos en otros ámbitos médicos, como la segmentación del músculo pectoral en mamografías o la segmentación de la arteria pulmonar en CTA. Actualmente, se está llevando a cabo la validación del algoritmo de segmentación de AAA 3D propuesto en esta tesis, con el objetivo de integrarlo en un producto comercial.
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Jagadesham, Vamshi Pulloori. "NK cell mediated lysis of vascular smooth muscle cells in abdominal aortic aneurysms." Thesis, University of Leeds, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.578645.
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Abdominal aortic aneurysms (AAA) are characterised by a chronic inflammatory infiltrate within the abdominal aortic wall and aortic smooth muscle cell (AoSMC) apoptosis. It is postulated that the inflammatory infiltrate causes AoSMC apoptosis, with resultant aortic wall weakening and aneurysmal degeneration. This putative immune-mediated reaction against aortic wall component suggests that AAA may have features of an auto immune disease. It has been previously demonstrated that natural killer (NK) cells are elevated in the peripheral blood (PB) of AAA patients and display increased cytotoxicity against AoSMC. This study aimed to identify the molecular basis of the increased NK cell cytotoxicity and why an immune-mediated reaction occurs against AoSMC. Using multi-parametric flow cytometry (FC), expression of the activatory receptors NKp30, NKp44, NKp46 and NKG2D were analysed on PB NK cells from AAA patients and age-sex-matched healthy controls. No difference in activatory receptor expression or cell surface density (ΔMFI) existed between the two groups. Region specific (intra-luminal blood and AAA tissue) activatory receptor phenotypes were also investigated in AAA patients. The significant finding was a reduction in the ΔMFI of NKG2D on tissue NK cells, suggesting an interaction between this receptor and potential cognate ligands within the aortic wall. Characterised AoSMC explanted from AAA tissue were subjected to analysis using qRT-PCR and FC to identify the expression of death receptors (Fas, TRAIL-RI and TRAIL R2) and NKG2D ligands (MICA, MICB, ULBPI-3). AoSMC expressed mRNA for all NKG2D ligands. FC confirmed the cell-surface expression of NKG2D ligands and the death receptors. A significantly greater percentage of NK cells from AAA patients were CD107a+ when co-cultured with AAA AoSMC, thus accounting for the increased cytotoxicity in this group. Despite using anti-NKG2D it was not possible to inhibit NK cell degranulation in response to the NKG2D ligands on AoSMC. This work has demonstrated that AoSMC from AAA express death receptors and NKG2D ligands, potentially accounting for the NK cell molecular mechanism that leads to AoSMC apoptosis. The expression of NKG2D ligands, which have been demonstrated in other auto immune diseases, favours the hypothesis that AAA are an immune-mediated process directed against the abdominal aortic wall.