Abstract
Objective To investigate the effect of angiotensin-converting enzyme 2(ACE2)over-expression on ventricular remodeling in rat model of acute myocardial infarction(AMI)and the related mechanisms.Methods Totally 75male SpragueDawley rats were randomly divided into five groups(n=15):Sham group,AMI group,AMI+normal saline(AMI+NS) group,AMI+adenovirus-EGFP(AMI+AdEGFP)group,and AMI+adenovirus-ACE2(AMI+AdACE2)group.AMI models were established by ligating the left anterior descending coronary artery of rats.Rats in the AMI+NS,AMI+AdEGFP and AMI+AdACE2groups received intramyocardial injection of NS,AdEGFP and AdACE2in five different infarction border zones,respectively.Rats in the Sham and AMI groups received no injection intervention.Four weeks later,left ventricular end-diastolic pressure(LVEDP)and heart weight/body weight(HW/BW)were examined.Myocardial structure changes and collagen deposition were evaluated histopathologically.The expression of angiotensin(Ang)Ⅱ(AngⅡ),Ang-(1-7)and α-smooth muscle actin(α-SMA)proteins was assessed by immunohistochemical staining.The relative protein expression of ACE2,Src homology 2domain-containing protein tyrosine phosphatase 1(SHP-1),ERK1/2,p-ERK1/2,p38,p-p38,α-SMA and transforming growth factorβ1(TGF-β1)was measured by Western blotting analysis.Results(1)Compared with the other four groups,the protein expression levels of ACE2 and Ang-(1-7)were significantly increased in myocardial tissues in AMI+AdACE2group(P0.05).(2)Compared with the Sham group,LVEDP,the values of HW/BW,collagen deposition,and the expression levels of AngⅡ,Ang-(1-7),SHP-1,p-ERK1/2/ERK1/2,p-p38/p38,α-SMA and TGF-β1were all signficantly upgraded in AMI,AMI+NS and AMI+AdEGFP groups(P0.05).(3)Compared with AMI,AMI+NS and AMI+AdEGFP groups,the expression levels of Ang-(1-7)and SHP-1were significantly increased in AMI+AdACE2group(P0.05);while p-ERK1/2/ERK1/2,p-p38/p38,α-SMA and TGF-β1protein expression levels were significantly decreased in AMI+AdACE2group(P0.05).Conclusion This study suggests that over-expression of ACE2can improve ventricular fibrosis and ameliorate ventricular remodeling after myocardial infarction in rats,which may be due to that ACE2increases SHP-1protein expression,and the latter negatively regulates renin-angiotensin system(RAS)and mitogen-activated protein kinases(MAKPs)pathway.
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