Pravastatin prevents myocardium from ischemia-induced fibrosis by protecting vascular endothelial cells exposed to oxidative stress.

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.