Cellular proliferation, cellular death and atherosclerosis.

The multipotential smooth muscle cell (SMC) is the predominant cell in arterial media and intima, and the major cell type involved in proliferative lesions. Studies using a precursor of DNA, namely [3H] thymidine, and autoradiography have shown that proliferation of SMC is an important and early response to atherogenic stimuli, such as cholesterol feeding, surgically induced hypertension or endothelial injury. Cultures of aortic SMC offer excellent in vitro models to study the reactivity of these cells to recognized or suspected risk factors. Pure SMC cultures are obtained by placing small fragments of aortic media in a defined culture medium and their response evaluated by thymidine incorporation and/or increase in size of the outgrowing cell colony. Factors essential for adequate growth include normal serum constitutents, including the lipoproteins and a platelet derived factor. Replacing the normal serum with dietarily induced hyperlipemic serum results in greatly increased proliferation. The serum fraction largely responsible for this phenomenon is the low density lipoprotein. Simultaneous addition of high density lipoproteins partly suppress this reaction. Serum from diabetic or hypertensive--but normolipemic--animals similarly stimulates these cells to increased proliferation.