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Title: The role of collagenases in atherosclerotic plaque instability
Author: Molloy, Kevin John
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2004
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The primary aim of this thesis was to quantify the collagenase concentrations in carotid plaques and to relate them to markers to plaque instability.;Recent studies have shown that strain therapy decreases cardiovascular risk, even in patients with normal cholesterol levels. A further aim of this thesis was to observe the effects of statins on clinical and biochemical indicators of plaque instability.;Atherosclerotic plaques were collected from 159 patients undergoing carotid endarterectomy. The presence and timing of carotid territory symptoms was ascertained. Pre-operative embolisation was recorded by transcranial Doppler. Each plaque was assessed for histological features of instability. Plaque MMP and cytokine concentrations was quantified using ELISA.;Significantly higher concentrations of active MMP-8 were observed in the plaques of symptomatic patients (p=0.0002), emboli-positive patients (p=0.0037) and in those plaques demonstrating histological evidence of rupture (p=0.0036). No differences were seen in the levels of MMP-1 and MMP-13. Immunohistochemistry, in situ by hybridisation and colocalisation studies confirmed the presence of MMP-8 protein and mRNA within the plaque, which colocalised with macrophages. These data suggest that the active form of MMP-8 may be partly responsible for degradation of the collagen cap of atherosclerotic plaques. This enzyme represents an attractive target for drug therapy aimed at stabilising vulnerable plaques.;Patients on statins were less likely to have suffered symptoms in the month prior to surgery (p=0.0049) and less likely to have cerebral embolisation detected (p=0.0459). Carotid plaques retrieved from statin-taking patients, revealed significantly lower concentrations of MMP-9 (p=0.0018) and IL-6 (p=0.0005). These data suggest that statins may stabilise plaques by lowering MMP and cytokine levels, resulting in decreased embolisation and symptoms.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available