The experimental study of the benificial effects of simvastatin on ventricular remodeling induced by TGFβ1 via Smad3 signal pathway

Aim To investigate the beneficial effects of simvastatin on ventricular remodeling in rats after myocardial infarction and its possible mechanisms.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 10 mg·kg-1·d-1 treatment group(Sim1,n=8),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,levels of serum lipids were measured.Effects of sinvastatin on ventricular remodeling 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 transforming growth factor β1(TGF-β1) and Smad3 in NIZ by Western blot and RT-PCR.Results(1) There were no significant differences betweem groups in levels of serum lipids(P0.05).Compared with those in Sham group,LVWI,the typeⅠCVF,type Ⅲ CVF andⅠ/Ⅲ ratio in NIZ were increased significantly in MI group.Compared with those in MI group,the LVWI,the type ⅠCVF,type Ⅲ CVF andⅠ/Ⅲ ratio in NIZ were decreased significantly in Sim groups(but higher than those in Sham group).Compared with MI groups,left ventricular function in rats treated with simvastatin was also obviously improved.(2) Contrasted to those in MI group,the expressions of TGF-β1 and Smad3 were down-regulated in simvastatin treatment groups(but higher than those in Sham group).Conclusions Sim can ameliorate ventricular remodeling and ventricular function in rats induced by MI,and the mechanisms can be independent of its lipid-lowering and associated with inhibition of TGF-β1/Smad3 signal transduction.