The Effect Of Simvastatin On Osteopontin Expression And It's Relationship With Ventricular Remodeling In Rats After Myocardial Infarction

Background and Objective: The remodeling of extracellular matrix(ECM) is the one of most important factor during the ventricular remodeling after myocardial infarction(MI). OPN and MMPs play a key role in this system. Some studies have demonstrated that osteopontin levels increase after MI. Meanwhile, some investigations also have demonstrate that Statins can degrade osteopontin expression in kidney and aorta diseases. So the aims of this study were to assess the effects of Simvastatin (Sim) on osteopontin expression in rats with an experimental MI, analyze the relationship between the difference of OPN and MMPs expression and explore its mechanism.Method: MI models was maded in Wistar rats by ligation of the left anterior descending coronary artery. Rats with extensive MI were randomized to treat with placebo or Sim (40mg/kg/d) as via gavage for 4 weeks starting on the 1th post-operation day. There were three groups: Sim group, MI control group , Sham group. Infarcted size, cholesterol levels,left and right ventricular weights, index of weight, index of echocardiogram were recorded after 4 weeks. The gene expression of OPN,MMP-2 and MMP-9 were detected by RT-PCR. The expression of OPN,MMP-2 and MMP-9 protein were detected by immunohistochemistry and western bloting.Results:①Infarct size and cholesterol levels were similar among all groups(P>0.05).②Placebo-treated infracted rats (MI control group) developed significant increase in left/right ventricular weight index, compared with Sham group (P<0.01), in Sim group rats, a significant reduction of left/right ventricular weight index was founded (P<0.05 versus MI control group).③Left ventricular posterior wall thickness(LVPWT) was thickening in rats on placebo (P<0.01 versus Sham group), and it was significantly amendment by Sim treatment (P<0.05 versus MI control group). Left ventricular end diastolic dimension(LVDd) was wide in rats on placebo (P<0.01 versus Sham group), and it was significantly amendment by Sim treatment (P<0.05 versus MI control group). FS and LVEF were decreased in MI control group (P<0.01 versus Sham group), while it was significantly increased by Sim treatment (P<0.05 versus MI control group).④The mRNA expression of OPN,MMP-2 and MMP-9 was significantly up-regulated in MI control group, and it was significantly down-regulated in Sim groups.⑤The protein level of OPN,MMP-2 and MMP-9 increased in MI control group (P<0.01 versus Sham group), and it was significantly attenuated in group (P<0.05 versus MI control group).⑥There was significantly positive correlation between the changes of OPN and ventricular weight index (r=0.760, P=0.029;r=0.804,P=0.016), a negative correlation between the changes of OPN and echocardiogram index (LVEF,FS) was founded in MI control group (r=-0.791,P=0.020;r=-0.841,P=0.009), and significantly positive correlation in the changes of OPN,MMP-2 and MMP-9 in Sim group was founded (r=0.784,P=0.021;r=0.730,P=0.039).Conclusion: Myocardial remodeling happened in cardiac tissue after MI;The osteopontin may be responsible for myocardial remodeling, and Sim can inhibit its function,then inhibit MMP-2 and MMP-9 activation ,so Sim have protect propert for myocardial remodeling.