Simvastatin inhibits RhoA translocation and Rho GTPase activity and prevents cardiac hypertrophy in chronic heart failure rabbit models

AIM: To investigate the effects of simvastatin on cardiac hypertrophy and the mechanism in chronic heart failure rabbit models. METHODS: Twenty four New Zealand rabbits were divided into four groups. Group I was designated the normal control group with sham operation. In the other three groups, aortic regurgitation and coarctation of ascending aorta were performed. Group II was designated the heart failure control group, Group III was the early treatment group ［simvastatin 5 mg/(kg·day) postoperatively for 8 weeks］ and Group IV represented the late treatment group ［simvastatin 5 mg/(kg·day) 4 weeks postoperatively for 4 weeks］. On weeks 0 and 8, echocardiographic evaluations were performed. At the eighth postoperative week, heart weight (HW), left ventricular weight (LVW), body weight (BW), heart weight/body weight ratio (HW/BW ratio), and left ventricular weight/body weight radio (LVW/BW ratio) were measured. RhoA expression in cardiomyocyte membrane was analyzed by Western blotting, and Rho GTPases activity was determined by ［γ-32P］ GTP-binding assays. RESULTS: Compared with those in the heart failure control group, IVST, LVIDd, LVPwd, LVIDs, HW, LVW and HW/BW ratio were significantly lower but ejection fraction and fractional shortening were significantly higher in the early and late treatment groups. LVW/BW ratio in the early treatment group was significantly lower than in the heart failure control group. RhoA expression in cardiomyocyte membrane and GTPase activity in the heart failure control group were significantly higher than those in the normal control group but RhoA expression in cardiomyocyte membrane and GTPase activity in early and late treatment groups were significantly lower than in the heart failure control group. CONCLUSION: Simvastatin inhibits the translocation of RhoA from heart cell cytosolic to membrane and thus decreases the activity of Rho GTPase, possibly by reversing left ventricular remodeling and keeping cardiac functions of CHF rabbit model.