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 r isk factor of atherosclerosis in epidemiological and experimental stud ies. Since intimal hyperplasia in vascular tissue is an important comp onent of atherosclerosis, we examined the effect of cadmium on the pro liferation of vascular smooth muscle cells cultured in a serum-free me dium. It was found that cadmium at 100 nM or less can increase the inc orporation of [H-3]thymidine into the acid-insoluble fraction of growi ng bovine and rabbit aortic smooth muscle cells but not of growing bov ine aortic endothelial cells. Although vascular smooth muscle cells ar e sensitive to cadmium cytotoxicity, no increase in the leakage of lac tate 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 signi ficantly increased by cadmium. It was therefore suggested that low lev els 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 fact or of atherosclerosis through dysfunction of vascular smooth muscle ce lls as well as vascular endothelial cells under certain conditions. (C ) 1998 Elsevier Science Ireland Ltd. All rights reserved.