Oxysterol-induced apoptosis of vascular smooth muscle cells is reduced by HMG-CoA reductase inhibitor, pravastatin.

Abstract

We investigated the mechanism by which 7-ketocholesterol damages vascular smooth muscle cells and the protective effect of the hydroxymethyl glutary CoA reductase inhibitor, pravastatin on it. When 7-ketocholesterol (50 micromol/L) was added to cultured human vascular smooth muscle cells, the extent of cell detachment increased and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling was positive. DNA extracted from the smooth muscle cells exposed to 7-ketocholesterol showed a ladder pattern on agarose electrophoresis. The fragmented DNA also increased in smooth muscle cells incubated with 7-ketocholesterol dose-dependently. In the presence of pravastatin, the cell detachment induced by 7-ketocholesterol was inhibited and the amount of fragmented DNA decreased significantly. These effects of pravastatin were inhibited by mevalonate. The results suggest that 7-ketocholesterol-induced apoptosis of vascular smooth muscle cells is inhibited by pravastatin, and mevalonate acts as a trigger of the apoptosis.