This project will investigate the in vitro cellular senescence of vascular endothelial cells which have been subjected to mechanical forces and its effects on matrix synthesis. Our rationale for these studies is: (1) since atherosclerosis is a major disease involving connective tissue changes whose incidence is significantly higher in older individuals, and since the major cell types affected are endothelial and smooth muscle cells, it is appropriate to determine the relation between matrix synthesis and aging, (2) atherosclerotic changes occur over a long time frame (years) and our system will permit us to model this time frame in vitro, and (3) the mechanism by which mechanical stimulation may affect cell metabolism and protein synthesis remains to be elucidated. In the present study, we plan to utilize vascular cells to examine several other specialized functions of endothelium. We will investigate the rate of synthesis of matrix proteins such as collagen and fibronectin. In addition, we will investigate the effects of mechanical forces on these rates throughout their replicative life-span. We will also determine if application of mechanical forces alters the in vitro life-span of these cells. We will also determine if a redistribution of matrix components occurs in mechanically strained or stressed cells by using immunohistochemistry. Light and electron microscopic studies will be carried out to evaluate these changes.
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