Effect of simvastatin on endothelial cell apoptosis mediated by Fas and TNF-α

摘要: Although there is evidence suggesting that statins may exert an endothelial protecting effect, recent in vitro data have shown these compounds induce cells (EC) apoptosis. We previously reported the Fas-death receptor apoptosis of liver sinusoid (LSEC), and TNF-α increases susceptibility to suffer Fas-mediated Based on this evidence, study, we investigated effect simvastatin LSEC Simvastatin induced a significant reduction viability, dose dependent manner, under serum-containing or serum-free conditions. This was prevented by mevalonate GGPP, indicating role hydroxy-3-methylglutaryl-CoA reductase. The death not associated with increased activation caspase-3. found mediated Fas. Further, LSEC-apoptosis Fas TNF-α. Mevalonate GGPP partially simvastatin-induced sensitization Jo2 TNF-α, but alone. did up-regulation LSEC. Our results provide modulating cells. These clinical implications those conditions high levels FasL