The purpose of this project is to test the hypothesis that aging alters processes central to the pathogenesis of atherosclerosis: (1) the proliferative responses of the key cells involved in atherogenesis, smooth muscle cells and endothelial cells, and (2) the metabolism of low density lipoproteins (LDL) and the regulation of cellular cholesterol metabolism in arterial smooth muscle cells. We propose to test whether the proliferative response of cultured arterial smooth muscle cells and endothelial cells to growth factors and hormones is altered as a function of donor age and in vitro age. In addition, the influence of proliferation of arterial smooth muscle cells in vivo influences subsequent lifespan in cell culture. The regulation of LDL receptor activity, LDL degradation and cell cholesterol content will be tested as a function of donor age in human arterial smooth muscle cells in comparison to other cell types, to other ligands specifically bound to cell surface receptors, and to arterial smooth muscle cells from other species.