Effects of simvastatin on ventricular remodeling after myocardial infarction induced by TGF-β_1/TAK1 pathway in rat

Objective To investigate the beneficial effects of simvastatin on ventricular remodeling in rats after myocardial infarction and the possible mechanisms involved.Methods The myocardial infarction rat model was reproduced.Twenty-four hours after infarction,the survived rats were randomly divided into myocardial infarction group(MI group,n=9),simvastatin 10mg group [10mg/(kg·d),Sim1 group;n=8],simvastatin 20mg group [20mg/(kg·d),Sim2 group;n=10] and simvastatin 40mg group [40mg/(kg·d),Sim4 group;n=9].A sham-operated group(Sham group;n=10) served as control.Four weeks later,the serum lipid level,hemodynamic indexes and left ventricular weight index(LVWI) were measured.The changes in rats' myocardial tissue were observed with HE staining;the cross-sectional area of myocardial cells was calculated.The expressions of transforming growth factor β1(TGF-β1) and TGF-β-activated kinase 1(TAK1) in non-infarction area were determined by Western blotting and reverse transcription polymerase chain reaction(RT-PCR).Results The hemodynamic indexes,LVWI,cross-sectional area of myocardial cells and the pathological changes were improved,and mRNA and protein expressions of TGF-β1 and TAK1 were down-regulated significantly in the 3 Sim-treated groups compared with that in MI group.The indices mentioned above were significantly different in Sim2 and Sim4 group compared with Sim4 group(P0.05),while no significant difference was found in serum lipid levels among all the groups(P0.05).Conclusion The inhibitory effect of simvastatin on ventricular remodeling after acute myocardial infarction is independent of its lipid-regulating effect,but possibly attributed to its action in inhibiting the TGF-β1/AK1 signal transduction.Within the concentration of 20mg/(kg·d),the therapeutic efficacy of simvastatin may be more obvious with an increase in its dosage.