The long-term goal of this project is to identify characteristic features of the vulnerable plaque, defined as an atherosclerotic lesion that poses an increased risk for thromboembolic complications. In this proposal, we plan to study mechanisms that may lead to the development of the vulnerable plaque using high resolution MRI. To achieve these goals, we will serially examine a cohort of subjects with moderate carotid stenosis to identify changes in the MRI appearance of the artery as it evolves from a clinically silent, stable plaque to a symptomatic, culprit lesion. Histological studies suggest that the vulnerable plaque is characterized by thinning and rupture of the fibrous cap that overlies the thrombogenic necrotic core. Other studies also suggest an important role for plaque neovasculature. Neovessels within plaque are believed to represent a pathway for macrophage infiltration, and these macrophages have been shown to express matrix metalloproteinases that can weaken the fibrous cap. Previous studies have shown that MRI is capable of precisely measuring plaque volume, distinguish thick fibrous caps from thin or ruptured caps, and identify regions with plaque neovasculature.
The specific aims of this study are: 1. Test the hypothesis that fibrous cap thinning and rupture precedes increase in plaque volume 2. Test the hypothesis that plaques with increased neovasculature are more likely progress from a thick cap to a thin or ruptured cap lesion, and are more likely to demonstrate progression in plaque volume 3. Test the hypothesis that progression from a thick cap to a thin or disrupted cap lesion correlates with the onset of an ischemic neurological event or histological evidence of cap thinning or rupture. A better understanding of the mechanisms leading to the development of the vulnerable plaque may provide new targets for therapy. Furthermore, identification of additional high-risk plaque features, other than the degree of lumen stenosis, may lead to better selection of patients for intervention, such as carotid endarterectomy, and result in overall reduction in health care costs.
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