Oxysterols induced apoptosis in cultured smooth muscle cells through CPP32 protease activation and bcl-2 protein downregulation.

Previously we have shown that oxidized low density lipoprotein (Ox-LDL) induced apoptosis in vascular smooth muscle cells (VSMCs) and that this apoptosis contributed to oxysterol, 7-ketocholesterol. The aim in this present study was to identify the mechanism by which oxysterols induced apoptosis in VSMCs. We show that both 7-ketocholesterol and 25-hydroxycholesterol induced apoptosis, followed by a rapid decrease in bcl-2 protein in the cells. CPP32/Yamma inhibitor prevented apoptosis induced by 7-ketocholesterol and 25-hydroxycholesterol in VSMCs, whereas the exogenous cholesterol, which itself did not have any apoptotic activity, inhibited 25-hydroxycholesterol induced apoptosis but the 7-ketocholesterol-induced apoptosis was not affected. These results suggest that 25-hydroxycholesterol induced-apoptosis occurs by a different mechanism than 7-ketocholesterol induced-apoptosis.