Promotion of cultured vascular smooth muscle cell proliferation by low levels of cadmium.

Cadmium is a toxic heavy metal which has been shown to be a possible risk factor of atherosclerosis in epidemiological and experimental studies. Since intimal hyperplasia in vascular tissue is an important component of atherosclerosis, we examined the effect of cadmium on the proliferation of vascular smooth muscle cells cultured in a serum-free medium. It was found that cadmium at 100 nM or less can increase the incorporation of [3H]thymidine into the acid-insoluble fraction of growing bovine and rabbit aortic smooth muscle cells but not of growing bovine aortic endothelial cells. Although vascular smooth muscle cells are sensitive to cadmium cytotoxicity, no increase in the leakage of lactate dehydrogenase from the cells was caused by the metal at 200 nM or less in bovine aortic smooth muscle cells. Intracellular accumulation of radioactive calcium in bovine aortic smooth muscle cells was significantly increased by cadmium. It was therefore suggested that low levels of cadmium may promote the proliferation of vascular smooth muscle cells through intracellular calcium-dependent signalling pathway. The present study supports the hypothesis that cadmium can be a risk factor of atherosclerosis through dysfunction of vascular smooth muscle cells as well as vascular endothelial cells under certain conditions.