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Title: An investigation into the expression of matrix metalloproteinase-2 in the vasculature of patients with abdominal aortic aneurysms
Authors: Goodall, Stephen.
First Published: 2002
Award date: 2002
Abstract: The biochemical and pathological changes associated with aortic aneurysms have been well characterised. Aneurysms demonstrate arterial dilatation, wall thickening and dramatic reduction in the elastin / collagen ratio. These changes are accompanied by an inflammatory infiltrate and excessive production of matrix metalloproteinases (MMPs), which regulate widespread matrix degradation. However, despite extensive research aimed at characterising aneurysmal tissue, the agents responsible for initiating aneurysm formation remain elusive..;Recent evidence suggested that patients with AAA have a systemic disease of their vasculature that manifests as local aneurysmal dilation. These previous studies suggested that any biological process initiating localised aneurysm formation might be manifest throughout the entire vascular tree. Matrix metalloproteinase-2 (MMP-2) is the dominant elastase in small AAA, and overexpression of this enzyme by vascular smooth muscle cells (SMC) may be a primary aetiological event in aneurysm genesis. The aim of this study was to investigate MMP-2 production in vascular tissue remote from the abdominal aorta..;Inferior mesenteric vein (IMV) was harvested from patients with aneurysmal disease and age-matched controls. Tissue homogenates derived from patients with aneurysms demonstrated significantly elevated MMP-2 levels compared with the control group. Histological examination localised this elevated MMP-2 production to SMC within the medial layer, a characteristic maintained once SMC had been isolated in culture. It was demonstrated that these increased levels of MMP-2 resulted from over expression by SMC. In addition, SMC derived from AAA patients exhibited a greater migratory potential than those harvested from controls..;Histological examination revealed fragmentation of elastin fibres and a significant depletion of elastin within the media of venous tissue obtained from the AAA group. As a consequence, mechanical testing of IMV demonstrated that elastin fragmentation compromised vessel biomechanics, resulting in reduced stiffness and tensile strength..;It may be postulated that these alterations in biomechanics and migration result from MMP-2 upregulation. These data support both the systemic nature of aneurysmal disease, and a primary role of MMP-2 in aneurysm formation..
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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