Effects of Metoprolol on Cardiac Extracellular Matrix Remodeling in Acute Myocardial Infarction Rats

Objective:To investigate the roles of metalloproteinase(MMP-2),tissue inhibitor of metalloproteinase(TIMP-2) and transforming growth factorβ1(TGF-β1) in extracellular matrix remodeling after acute myocardial infarction and effects of Metoprolol on it in a rat model.Methods: Rats surviving 24h after AMI induced by left anterior descending branch ligation were randomized to Metoprolol and control groups compared with sham-operated group.Metoprolol group were given Metoprolol 50 mg/(kg·d).Control and sham-operated group were given saline 15 ml/(kg·d).The ventricular remodeling index,the expression of myocardium MMP-2,TIMP-2 and TGF-β1 proteins were observed or examined by immunohistochemical analysis in the AMI rats at 4 weeks.Results: Compared with sham-operated rats,the protein expression of MMP-2,TIMP-2 and TGF-β1 and MMP-2/TIMP-2 ratio were significantly increased(P0.01),while left ventricular(LV) end diastolic pressure(LVEDP),LV relative weight(LVRW),right ventricular relative weight(RVRW) and collagen volume fraction(CVF) were significantly increased(all P0.01);whereas-dp/dt,+dp/dt were significantly reduced(P0.01) at 4 weeks after AMI,indicating decreased LV remodeling and LV function.After four-week metoprolol treatment,the protein expression of MMP-2,and TGF-β1 and MMP-2/TIMP-2 ratio were significantly reduced,respectively from 0.281,0.253 and 1.836 to 0.153,0.128 and 1.006(all P0.01),while left ventricular(LV) end diastolic pressure(LVEDP),LV relative weight(LVRW),right ventricular relative weight(RVRW) and collagen volume fraction(CVF) were significantly reduced by 36.13%,9.56%,9.95% and 29.06%(all P0.01),whereas-dp/dt,+dp/dt were significantly increased by 8.90%,9.64%(all p 0.01) at 4 weeks after AMI.Conclusion: Metoprolol may prevent left ventricular extracellular matrix remodeling,which is associated with the attenuation of myocardial MMP-2 and TGF-β1 and the reversion of MMP-2/TIMP-2 balance.