Effect of carvedilol on extracellular matrix remodeling and matrix metalloproteinase after myocardial infarction in rabbits

AIM: To investigate the effect on myocardial extracellular matrix remodeling and matrix metalloproteinases(MMPs) after myocardial infarction(MI) in rabbits by carvedilol which is third-generation β adrenoceptor antagonist.METHODS: Thirty-six New Zealand white rabbits were randomized to 3 groups(n=12): MI group,MI + carvedilol group and sham-operation group.The models of MI were induced by ligation of left ventricular branch;the sham-operation group was made by the same(procedure) but no ligation.The rabbits were killed 4 weeks after operation to examine hemodynamic parameters,body weight(BW),left and right ventricular weight(LVW,RVW).Collagen volume fraction(CVF) was measured by using Van Gieson (VG) in noninfarcted region;the protein expressions of matrix metalloproteinase 2(MMP-2) and matrix metalloproteinase 9(MMP-9) were detected by immunohistochemical analysis in noninfarcted myocardium,and the MMPs activities were assessed by zymography.RESULTS: At week 4 after MI,there were 8(rabbits) left in MI group,9 in MI+carvedilol group and 10 in sham-operation group.Compared with the sham-operation group,RVW/BW,LVW/BW,left ventricular end-diastolic pressure(LVEDP) and CVF were increased significantly,and expressions and activities of MMP-2 and MMP-9 were enhanced in non-(infarcted) myocardium of MI group(P0.01).Compared with the MI group,RVW/BW,LVEDP and CVF were decreased(significantly)(P0.05-0.01),and expressions and activities of MMP-2 and MMP-9 were weakened in the MI + carvedilol group(P0.05-0.01).CONCLUSION: Carvedilol can prevent myocardial extracellular matrix remodeling,which is associated with the attenuation of myocardial MMP-2 and MMP-9 expressions and activities.