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Title: The role of matrix mellaproteinases in cartoid plaque morphology
Author: Loftus, Ian Magnus
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2001
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Thromboembolic disease secondary to atherosclerosis is the commonest cause of myocardial infarction and ischaemic stroke. The atherosclerotic plaque develops into a complex structure consisting of a lipid rich core and a connective tissue matrix. If the plaque undergoes acute change such as rupture or ulceration, exposure of highly thrombogenic material in the plaque core leads to thrombus formation with subsequent embolisation or vessel occlusion. There is considerable evidence to support the theory that such acute changes immediately precede the onset of clinical symptoms. Targeting pharmacotherapy towards preventing acute plaque change could in theory reduce the risk of stroke and myocardial infarction in patients with atherosclerosis. The potential for therapeutic intervention to prevent disease progression is therefore a very attractive option, but the precise cause of acute plaque disruption and thus the target for pharmacotherapy, has been elusive. There is increasing evidence that a group of proteolytic enzymes called matrix metalloproteinases (MMPs) are intimately involved in the atherosclerotic disease process. The plaque is a dynamic structure, undergoing continuous remodelling of the extracellular matrix upon which its structural integrity depends. 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. The hypothesis in this study of was that a localised imbalance in the level of MMPs and their inhibitors may be associated with plaque instability and the onset of clinical events. The aim of the study was to quantify the major MMP/TIMP subtype levels within carotid plaques and to correlate them with clinical and histological features of plaque instability.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available