Abstract
Lead is a heavy metal which has been experimentally and epidemiologically shown to induce vascular lesions such as atherosclerosis, however, little is known about the mechanism. Since damage of endothelial cell layers is a key event in the initiation of atherosclerosis, the effect of lead on the maintenance of cell layers has been studied using a cell culture system in our laboratory. The following results were obtained : (1) Endothelial cell monolayers are not destroyed but the repair after injury is markedly inhibited by lead through inhibition of the proliferation. (2) Lead suppresses the proliferative response of endothelial cells to basic fibroblast growth factor (bFGF). (3) Lead reduces the amount of endogenous bFGF bound to heparan sulfate proteoglycans through inhibition of the synthesis of perlecan, a large heparan sulfate proteoglycan. Since heparan sulfate chains of perlecan promote the binding of bFGF to its receptor, our results indicate that inhibition of the repair of injured endothelial monolayers by lead is due to a lower proliferative response of the cells to endogenous bFGF, caused by a suppression of perlecan synthesis.
