The relationship simvastatin regulating Smad7 expression with its effect of ameliorating ventricular remodeling in post-myocardial infarction rat

Objective:To assess the efects of simvastatin on ventricular remodeling in rats after myocardial infarction and to investigate the alternation of the expression of smad7 on myocardium.Method:Twenty-four hours after myocardial infarction by left anterior descending coronary artery ligation,the survival rats were randomly divided into myocardial infarction group(MI,n =9),simvastatin 20 mg·kg-1 ·d-1 treatment group(Sim2,n =10) and simvastatin 40 mg·kg-1 ·d-1 treatment group(Sim4,n =9).Sham-operated animals underwent identical surgery except for the coronary artery ligation(Sham,n =10).After 4 weeks,the effects of sinvastatin on myocardial fibrosis were evaluated by detecting changes of left ventricular weight index(LVWI),the collagen volume fraction(CVF) in non-infarction zone(NIZ) with Picric-Sirius Red Polarimetry,and the expressions of Smad7 in NIZ by immunohistochemical staining and reverse transcription polymerase chain reaction(RT-PCR).The myocardial histopathology was also examined by HE staining and an electron microscope.At the same time,levels of serum lipids were measured.Result:There were no significant differences in all groups in levels of serum lipids(P 0.05).Comparing with Sham group,LVWI,the typeⅠCVF,type Ⅲ CVF and the Ⅰ/Ⅲ ratio in NIZ were increased significantly in MI group.Comparing with MI group,the LVWI,the type ⅠCVF and type Ⅲ CVF in NIZ and the Ⅰ/Ⅲ ratio were decreased significantly in Sim groups,but higher than those in Sham group.Compared with MI groups,the histological changes of fibrosis and the ultrastructural alterations in rats treated with simvastatin were also obviously improved.Contrasted to MI group,the expressions of Smad7 were significantly increased in Sim groups.Conclusion:simvastatin has a protective effect on myocardial injury and can ameliorate myocardial fibrosis in rats induced by MI.The mechanisms of simvastatin anti-fibrosis could be independent of its lipid-lowering and associated with its effects of up-regulating Smad7.