Effect of simvastatin on cardiac hypertrophy in rabbits with chronic heart failure

Objective To study the effects of simvastatin on cardiac hypertrophy and cardiac function in rabbits with chronic congenital heart failure(CHF).Methods Twenty-four New Zealand rabbits were divided into 4 groups of A,B,C and D with 6 rabbits each.Group D underwent sham operation as healthy control.After establishment of CHF,the rabbits in group A were given oral simvastatin 5 mg·kg-1·d-1 after the operation for 8 weeks,those in group B were given oral simvastatin 5 mg·kg-1·d-1 for 4 weeks started at 4 weeks after the operation,and those in group C were not given simvastatin as the controls.At the end of experiment,heart weight(HW),left ventricular weight(LVW),body weight(BW),heart weight/body weight radio(HW/BW radio),left ventricular weight/body weight radio(LVW/BW radio)were measured.Rho A expression in cardiomyocyte membrane was detected with Western blot.Rho GTPases activity was determined by [γ-32P] GTP-binding assay.Results Compared to groups of A and B,the HW,LVW,HW/BW radio,and LVW/BW radio were significantly higher and the IVSD,LVIDs,LVPWd and LVIDd were significantly increased in group C(P0.01,P0.05).The EF and FS were significantly lower in CHF groups than those in group D(P0.01,P0.05).The expression of Rho A in cell membrane and the activity of Rho GTPase were significantly higher in group C than those in the other 3 groups(P0.01).Conclusion Simvastatin can inhibit cardiac hypertrophy and improve cardiac function by depressing the expression of Rho A in heart cell membrane and decreasing the activity of Rho GTPase in rabbits model with CHF.