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首页> 外文期刊>Cytokine >Effect of simvastatin on endothelial cell apoptosis mediated by Fas and TNF-alpha.
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Effect of simvastatin on endothelial cell apoptosis mediated by Fas and TNF-alpha.

机译：辛伐他汀对Fas和TNF-α介导的内皮细胞凋亡的影响。

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Although there is evidence suggesting that statins may exert an endothelial protecting effect, recent in vitro data have shown that these compounds may induce endothelial cells (EC) apoptosis. We previously reported that the Fas-death receptor may induce apoptosis of the liver sinusoid endothelial cells (LSEC), and that TNF-alpha increases the susceptibility of these cells to suffer Fas-mediated apoptosis. Based on this evidence, in this study, we investigated the effect of simvastatin on Fas-mediated LSEC apoptosis. Simvastatin induced a significant reduction in LSEC viability, in a dose dependent manner, under serum-containing or serum-free conditions. This effect was prevented by mevalonate and GGPP, indicating the role of hydroxy-3-methylglutaryl-CoA reductase. The simvastatin effect on LSEC death was not associated with increased activation of caspase-3. We found that simvastatin increased the susceptibility of LSEC death mediated by Fas. Further, simvastatin increased LSEC-apoptosis induced by Fas and TNF-alpha. Mevalonate and GGPP partially prevented simvastatin-induced sensitization to LSEC death mediated by Jo2 and TNF-alpha, but not Jo2 alone. Simvastatin did not induce up-regulation of the Fas on the LSEC. Our results provide evidence of simvastatin in modulating Fas-mediated apoptosis in endothelial cells. These results may have clinical implications in those clinical conditions associated with high levels of FasL and TNF-alpha.
机译：尽管有证据表明他汀类药物可能发挥内皮保护作用，但最近的体外数据显示这些化合物可能诱导内皮细胞（EC）凋亡。我们以前曾报道过Fas-death受体可能诱导肝窦内皮细胞（LSEC）凋亡，而TNF-α会增加这些细胞遭受Fas介导的细胞凋亡的敏感性。基于这一证据，在本研究中，我们研究了辛伐他汀对Fas介导的LSEC凋亡的影响。在含血清或无血清条件下，辛伐他汀以剂量依赖性方式诱导LSEC活力显着降低。甲羟戊酸和GGPP阻止了这种作用，表明了羟基-3-甲基戊二酰辅酶A还原酶的作用。辛伐他汀对LSEC死亡的影响与caspase-3激活的增加无关。我们发现辛伐他汀增加了由Fas介导的LSEC死亡的易感性。此外，辛伐他汀增加了由Fas和TNF-α诱导的LSEC凋亡。甲羟戊酸和GGPP部分阻止了辛伐他汀诱导的对Jo2和TNF-α介导的LSEC死亡的致敏作用，但不能单独阻止Jo2。辛伐他汀未在LSEC上诱导Fas上调。我们的结果提供了辛伐他汀调节Fas介导的内皮细胞凋亡的证据。这些结果可能在与高水平的FasL和TNF-α相关的临床状况中具有临床意义。

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