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Lead and cadmium are toxic heavy metals that have been shown to be possible risk factors of atherosclerosis in epidemiological and experimental studies. Since excess extracellular matrix, including proteoglycans, accumulates changing the composition and the structure in the atherosclerotic vascular wall, the effects of lead and cadmium on the proteoglycan synthesis in vascular cells have been studied using a cell culture system. The following results were obtained: Lead does not destroy endothelial cell layers but markedly inhibits the repair of the injured cell layers, which results from a lower response to endogenous basic fibroblast growth factor caused by inhibition of the synthesis of perlecan, a large heparan sulfate proteoglycan, in vascular endothelial cells. Lead selectively inhibits the synthesis of versican, a large chondroitin sulfate proteoglycan, in vascular smooth muscle cells only at a high cell density. Cadmium induces the synthesis of biglycan and decorin, small dermatan sulfate proteoglycans, in vascular smooth muscle cells only at a low cell density, while inhibiting the synthesis of other proteoglycan molecules. It is therefore suggested that lead and cadmium may influence the developmental process of atherosclerosis through disrupting the regulation of proteoglycan synthesis in vascular cells.

Cell Biological Study on Abnormal Proteoglycan Synthesis in Vascular Cells Exposed to Heavy Metals