Pravastatin prevents myocardium from ischemia-induced fibrosis by protecting vascular endothelial cells exposed to oxidative stress
Pravastatin prevents myocardium from ischemia-induced fibrosis by protecting vascular endothelial cells exposed to oxidative stress
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DOI：
10.1007/s10557-006-9525-7
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发表时间：
2006-08-01
影响因子：
3.4
通讯作者：
Mochizuki, Seibu
中科院分区：
文献类型：
--
作者：
Abe, Yuichi;Izumi, Takehiko;Mochizuki, Seibu
假设他汀类药物除了慢性抑制胆固醇合成外，还能有效防止心肌细胞急性缺血。我们研究了普伐他汀对心肌梗死（MI）后心功能的保护作用。方法对心肌缺血组（MI组）和普伐他汀组（MI/他汀组）进行超声心动图比较，发现心肌缺血组（MI/他汀组）心肌收缩力有统计学保护，而心肌缺血组（MI组）心肌收缩力下降。结果组织化学分析显示普伐他汀对缺血性心肌纤维化有预防作用。由于两组间没有明显的肌细胞凋亡反应肌细胞损失，缺血间质纤维化可能影响收缩力。结论我们推测他汀类药物可能直接影响血管内皮细胞调节心肌血供，而不是影响肌细胞。普伐他汀干扰h2o2诱导的内皮细胞NOS减少，抑制h2o2增加的血管内皮细胞caspase-3活化。这些数据表明普伐他汀通过作用于血管内皮细胞来预防心功能障碍。此外，急性心肌梗死患者早期给予普伐他汀可能有利于预防缺血相关纤维化引起的心肌损害。
Hypothesis Statins potently prevents cardiac myocytes from acute ischemia besides chronic inhibition of cholesterol synthesis. We investigated how pravastatin preserves the cardiac function after myocardial infarction (MI).Methods Echocardiographically comparing rats with myocardial ischemia (MI group) with those treated with pravastatin (MI/statin group), we found that cardiac contractility was statistically preserved in the MI/statin whereas it was deteriorated in MI group. Results Histochemical analysis suggested that ischemia-induced cardiac fibrosis was prevented by pravastatin. Because there was no significant myocyte apoptosis reflecting myocytes loss between two groups, ischemia-induced interstitial fibrosis might affect the contractility.Conclusion We hypothesized that statin may directly affect vascular endothelial cells regulating blood supply to the myocardium rather than affecting myocytes. Pravastatin perturbed H2O2-induced endothelial NOS reduction and inhibited H2O2-increased caspase-3 activation in cultured vascular endothelial cells. These data suggested that pravastatin prevent cardiac dysfunction by acting on vascular endothelial cells. Furthermore, early administration of pravastatin to the patients during acute onset of myocardial infarction may be beneficial to prevent myocardial damage caused by fibrosis associated with ischemia.