Simvastatin Prevents Cardiac Hypertrophy Induced By Myocardial Infarction Via Rho Kinase And Inhibition Of Cyclin D1

Objective: to study the inhibition effect of simvastatin on cardiac hypertrophy induced by myocardial infarction,and to investigate whether simvastatin prevent cardiac hypertrophy through attenuation of RhoA/ROCK and cyclin D1.Methods: male wistar rats were randomly divided into four groups(n=8). The sham operation group (SHAM) and the infarction group (MI group) were lavaged with 1ml NS once a day. The infarction+ simvastatin group (SIM group) was lavaged with simvastatin (40mg/kg.)once a day. And the infarction+specific ROCK inhibitor Fasudil group (F group) was peritoneal injected with Fasudil(7.5mg/kg) twice a day. At the timepoint of 28d,the ratio of LV weight to body weight(LVW/BW) and the surface area of cardiomyocytes were measured. The mRNA expression level of ROCK and cyclin D1 were detected by RT-PCR. The expression level of phosphorylated ERM and Cyclin D1 were detected by immunohistochemistry and Western blot. Results: at the point of 28d, all the indexes mentioned above significantly increased in the MI group compared with those in the SHAM group(P<0.05). And the indexes significantly decreased in the SIM group compared with those in the MI group(P<0.05) ,and F group showed the same results(P<0.05)Conclusion: simvastatin prevents postinfarct cardiomyocyte hypertrophy in part through inhibition of cyclin D1, which is linked to ROCK.