Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/29521
Title: Molecular and clinical observations in abdominal aortic aneurysm pathogenesis and treatment
Authors: Wilson, W. Richard W.
First Published: 2006
Award date: 2006
Abstract: The rupture of an abdominal aortic aneurysm is associated with a mortality of 60-70% and accounts for approximately 8000 deaths per year in men over 60 years of age in the United Kingdom. Aneurysm formation is clinically silent until, with increasing diameter, rupture occurs. At a cellular level, aneurysm formation is associated with an atherosclerotic or inflammatory trigger. An initial loss of elastin and smooth muscle cells from the aneurysm wall causes early aortic dilatation. Continued expansion and rupture is thought to be due to the loss of collagen mediated via either a global or local up-regulation of extracellular collagenase activity. A putative collagenase has not been identified for this process. Matrix metalloproteinases (MMPs) represent the main physiological regulators of the extracellular matrix, and any imbalance between the level of MMPs and their inhibitors could cause increased matrix degradation. Indeed there is sound evidence to suggest that MMP-2 and -9 are intimately involved in the degradation of elastin as part of aneurysm formation. The hypothesis of this study was that a potent collagenase, MMP-8, exists in the aneurysm wall and its expression is elevated over that found in the normal aorta. The action of this collagenase is increased further in the rupture process and is associated with an increase in inflammatory cell infiltration. The aim of this study was to quantify MMP-8 in normal aorta, to quantify other MMPs, TIMPs and inflammatory cell subtypes in abdominal aortic aneurysms and to correlate this with the clinical presentation of the aneurysm either non-ruptured or ruptured.
Links: http://hdl.handle.net/2381/29521
Type: Thesis
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Theses, College of Medicine, Biological Sciences and Psychology
Leicester Theses

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