Atherosclerosis is a vascular disease that is a primary cause of heart attack and stroke. It is becoming clear that abnormal migration of smooth muscle cells from their normal locations in the interior of the arterial wall to the inner layer close to the lumenal surface and subsequent division of newly accumulated smooth muscle cells are key events in the pathogenesis of atherosclerosis and arteriosclerosis. The long-term goal of this proposal is to study the mechanisms by which vascular smooth muscle cell migration is inhibited in healthy arteries, but stimulated under pathological conditions. Recently, we have found that the cancer cell suppressors, p53 and PTEN, also play a crucial role in inhibiting smooth muscle cell movement and may regulate pathogenesis of atherosclerotic plaques. This finding suggests a commonality in the mechanisms regulating cancer cell and vascular smooth muscle cell migration. Knowledge gained from this research will help us define the mechanisms by which vascular smooth muscle cell migration is regulated at the molecular level and will provide information for future designs of drugs to combat atherosclerosis and arteriosclerosis