Although research in atherosclerosis has focused on mechanisms of initiation, relatively little attention has been given to the more pressing problems of disease progression and recurrence after vascular reconstruction. There are two major objectives in the SCOR: to develop an understanding of how carotid atherosclerotic plaques enlarge and at a certain point become the cause of thromboembolic events; and to explore various aspects of the reparative response and the recurrence of lumenal narrowing after endarterectomy. Four of the projects will examine ultrasound characteristics of advanced atherosclerotic carotid and femoral lesions and endarterectomy-induced intimal thickening. These will be correlated with clinical symptoms and with the pathological characteristics of the excised surgical specimens. In addition, these lesions will be examined by in situ hybridization and Northern analysis for the expression of specific genes important for smooth muscle growth. Magnetic resonance imaging studies will be undertaken in vitro and in vivo model systems to develop better methods for the morphological and biochemical characterization of the human plaque. At the same time, animal models of disease progression and recurrent stenosis will be developed to define factors regulating smooth muscle proliferation and endothelial regeneration. In addition to an Administrative Core, the SCOR will have Morphology an? Image Analysis Cores to provide histological, immunocytological, and image procession support for the individual projects. The proposed studies will make use of a wide range of clinical basic research approaches, including ultrasound, MRI, light and electron microscopy, in situ hybridization, Norther analysis, analysis of cell cycle kinetics and modern approaches to growth factor biochemistry.
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