The Experimental Research Of Pleiotropic Protection Of Simvastatin On Myocardium

Statins (HMG-CoA reductase inhibitors) are used widely for the treatment of hypercholesterolemia. Recent studies of animals have demonstrated that statins could attenuate trauma induced by hypertension, resist fibrogenesis of myocardium with the help of angiotensin-converting enzyme inhibitor, prevent reconstruction of capillary in hypertrophic myocardium and reverse left ventricular hypertrophy. Howerver , the mechanisms need further investigating.Now, there are many views about the function of statins on cardiovascular regulation independent of cholesterol lowering, and proposed mechanisms include favorable effects on plasma lipoproteins, endothelial function and inflammation. An important one of those views is whether statins improve cardiovascular function through affecting calcium metabolism .We established rat models , including abdominal aorta contraction model and myocardial infarction model. Simvastatin, followed by investigation of heart function and apoptosis of myocardial cell, was administered . Study 1 Inhibiting effects of simvastatin on pressure overload-induced cardiac hypertrophy mediated by calcineurin. Sprague-Dawley rats were randomly allocated into three groups: The sham-operated groups(n=10), model groups(n=10) and simvastatin-treated groups(n=10). The model of pressure overload was established by abdominal arota constriction. At the end of the treatment period, the left ventricular weight/body weight ratio , left ventricular mass, wall thickness(by echocardiography) , myocardial content of CaN and CaNmRNA(by westernblot and RT-PCR) were assessed .Results:â‘ The left ventricular weight/body weight ratio of model group, as well as simvastatin-treated group , was significantly higher than sham-operated group(P<0.05); compared with model group, the ratio was lower in simvastatin- treated group(P<0.05).â‘¡The level of CaN and CaNmRNA expression in model group was higher, as compared to sham-operated group(P<0.01); significant higher level of CaN and CaNmRNA expression was observed in model group compared to simvastatin-treated group(P<0.05). We conclude that simvastatin may inhibit calcineurin and hypertrophy in rats with pressure-overload. Study 2 Protective effect of simvastatin against ventricular remodeling in postinfarction heart failure ratsSprague-Dawley rats were randomly allocated into three groups: The sham-operated groups(n=10), model groups(n=10) and simvastatin-treated groups(n=10). The model of myocardial infarction was established in order to cause heart failure. At the end of the treatment period, left ventricular end- diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), global left ventricular function ejection fraction (LVEF) and myocardial content of CaN (by westernblot) were assessed . RESULTS :â‘ The LVEF of model group, as well as simvastatin-treated group , was significantly lower than sham-operated group ( P<0.05 ) ; compared with model group, the ratio was higher in simvastatin-treated group(P<0.05).â‘¡The level of CaN expression in model group was higher, as well as simvastatin-treated group, as compared to sham-operated group(P<0.05); significant higher level of CaN expression was observed in model group compared to simvastatin-treated group(P<0.05).â‘¢The apoptosis ratio of model group was higher than that of sham-operated group(P<0.01); and the ratio of simvastatin-treated group was lower than that of model group ( P<0.05 ) . CONCLUSION: The present data suggest that simvastatin may inhibit calcineurin, hypertrophy and myocardial cell apoptosis in rats with heart failure and improve heart function.