rAAV-mediated angiogenin gene transfer induces angiogenesis and modifies left ventricular remodeling in rats with myocardial infarction.
In vitro studies have demonstrated that bovine angiogenin (ANG) significantly stimulates both the migration of endothelial cells and the formation of tubelike structures. The aim of this study was to explore whether ANG gene transfer could enhance vascularization, modify left ventricular remodeling, and attenuate cardiac dysfunction in rats with myocardial infarction (MI). We constructed a recombinant adeno-associated virus vector encoding the ANG gene (rAAV-ANG) and evaluated its angiogenic potential after regional transfection by intramyocardial injection immediately after left anterior descending artery ligation in rats. Four weeks after coronary artery ligation, rAAV-ANG transfection upregulated the myocardium ANG protein expression level in both normal and MI rats, and immunohistochemistry showed that the overexpressed ANG was distributed in the cytoplasm of cardiomyocytes. In rats with MI, rAAV-ANG treatment altered left ventricular remodeling, as indicated by a decrease in left ventricular end diastolic diameter, left ventricular end systolic diameter, cardiomyocyte diameter, ventricular weight to body weight ratio and interstitial fibrosis infiltration. We also found an increase in capillary density and partly restored cardiac function in the group receiving rAAV-ANG treatment. These results confirmed that in rats with MI, ANG gene transfer could induce angiogenesis, alter left ventricular remodeling, and attenuate cardiac dysfunction. This study provides a new choice of treatment for ischemic heart disease.
Zhao
Xiao-Yan
XY
Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People's Republic of China.
Hu
Shen-Jiang
SJ
Li
Jiang
J
Mou
Yun
Y
Chan
Chi-Fung
CF
Jin
Juan
J
Sun
Jian
J
Zhu
Zhao-Hui
ZH
D000818:Animals; D002417:Cattle; D000229:Dependovirus / Q000235:genetics*; D004452:Echocardiography; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D012259:Ribonuclease, Pancreatic / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D014162:Transfection; D020257:Ventricular Remodeling / Q000235:genetics*
C046366:angiogenin; D012259:Ribonuclease, Pancreatic