SMOOTH MUSCLE CELL APOPTOSIS

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Project 1 proposes that apoptosis plays a role in the formation of atherosclerotic lesions and in the ultimate narrowing of the vessel as lesions progress. The Specific Aims focus on the possible role of the cystein proteases and the Fas/FasL pathway in controlling cell death in vascular smooth muscle. This includes use of caspase inhibitors in animal models in which death has been thought to play a key role, and development of a transgenic mouse blocked at a common choke point determining death mediated via Fas and related receptors. These studies will include exploration of the role of death in controlling intramural coagulation, including two studies in vitro and in vivo to explore the possible role of fibrin gel contraction as a mechanism of vascular narrowing. Finally, selected human and mouse atherosclerotic tissues will be studied to determine the relevance of models based on molecules identified in vitro or in animal models.