The Effect Of Simvastatin On Left Ventricular Remodeling And Osteopontin Expression After Myocardial Infarction In Rats

Objective: Osteopontin(OPN), an extracellular matrix protein, plays a very important role in cardiac fibrosis.However, little is known about the effects of statins on OPN expression in non-infarcted myocardium. The purpose of this study was to elucidate the effects of Simvastatin and pyrrolidine dithiocarbamate(PDTC) on left ventricular remodeling and the expression of OPN in mycardium after myocardial infarction(MI).Methods: Rats survived after MI were divided into 3 groups: MI group(placebo, n=12); Sim group(Simvastatin 30 mg/kg per day, gavage, n=12); PDTC group(PDTC 100 mg/kg per day, gavage, n=12). In addition, Sham-operated group(n=12) was selected as the non-infarction control. 4 weeks later, infarct size, ventricular weight/body weight ratio, non-infarcted myocardial collagen volume fraction(CVF), hemodynamics, expression ofβ3 integrins, OPN, collagen I and NF-κB subunit P50 were investigated.Results: (1) Infarct size was Similar among MI group, Sim group and PDTC group(P>0.05). In MI group, ventricular weight/body weight ratio, CVF were all significantly higher(P<0.01) than those of Sham-operated group. For Sim group and PDTC group, ventricular weight/body weight ratio, CVF were all significantly lower (P<0.01) than those in MI group. (2)Both Simvastatin and PDTC can prevented the increase in LV end-diastolic pressure, and the reduction of LV +dp/dtmax and -dp/dtmax after MI(P<0.05 or P<0.01). (3)Expression ofβ3 integrins was increased(P<0.01) in MI group compare to Sham group. Expression ofβ3 integrins was significantly decreased in Sim group and PDTC group(all P<0.01). (4)For MI group, expression of OPN, collagen I and P50 were all significantly higher(P<0.05 or P<0.01) than those of Sham-operated group. Both Simvastatin and PDTC reduced OPN, collagen I and P50 expression compare to MI group(P<0.05 or P<0.01).Conclusions: Simvastatin inhibits OPN expression in non-infarcted myocardium and prevents ventricular remodeling after MI, and NF-κB involved in OPN expression after MI.