As the principle cause of myocardial infarction, strokes, and gangrene of the extremities, atherosclerosis is responsible for nearly half of all mortality in developed countries [l]. The excessive fibroproliferative response by vascular smooth muscle cells (VSMCs) to injury to the endothelium of the vessel wall contributes to the formation of the atherosclerotic lesion [2, 3]. In this process VSMCs migrate from the media into the intima and dedifferentiate and proliferate in response to growth factors released by endothelial cells, platelets, and macrophages [l-8]. A similar but more acute process occurs in artery restenosis, a complication that occurs in 25-50% of patients undergoing balloon angioplasty, and in the myointimal hyperplasia that is responsible for the vast majority of failures of prosthetic vascular bypass grafts. Eventually this uncontrolled proliferative response, whether acute or chronic, can lead to impingement on the lumen and compromise blood flow through the vessel or lead to thrombosis and distal tissue ischemia.

Unlike cardiac and skeletal muscle cells, which are terminally differentiated and incapable of further cell division, VSMCs retain the ability to re-enter the cell cycle in response to appropriate signals. The binding of peptide growth factors to cell surface receptors will initiate a cascade of intracellular signals that ultimately stimulates the cell to divide [6, 8-151. Upon re-entering the cell cycle, VSMCs activate certain genes [16] and down-regulate others, and in the process, also dedifferentiate and express lower levels of smooth-muscle-specific isoforms of contractile proteins and higher levels of non-muscle actins and myosins [10, 11, 13-1517-211 Presumably, transcription factors, whose expression is activated or repressed by serum mitogens, regulate the subordinate batteries of genes