Synergistically therapeutic effects of VEGF165 and angiopoietin-1 on ischemic rat myocardium

PURPOSE: The aim of this study was to determine whether the combination of 2 angiogenic growth factor, vascular endothelial growth factor 165(VEGF165) and angiopoietin-1 (Ang1), could increase angiogenesis and cardiomyocyte(CM) proliferation in an infarcted myocardium. METHODS: Myocardial ischemia was induced in rats by ligation of the left anterior descending (LAD) coronary artery. Replication-deficient adenoviruses encoding VEGF165 (Ad-VEGF165), Ang1 (Ad-Ang1) or enhanced green fluorescence protein (Ad-EGFP) was injected into the ischemic myocardium immediately. Bromodexyuridine (BrdU) was administered intraperitoneally 1 week after ligation. One week later, the hearts were harvested and sectioned for hematoxylin-eosin (HE) and immunohistochemistry to evaluate densities of capillary, arteriole and double labelled BrdU(+) CM. M-mode echocardiography was used to evaluate the cardiac function. RESULTS: Ang1 significantly increased collateral vessel formation. Both VEGF165 and Ang1 significantly increased densities of capillary and arteriole, as well as the number of double labelled BrdU(+) CM, and improved cardiac function. CONCLUSION: Our results suggest that the combination of VEGF165 and Ang1 can increase both myocardial angiogenesis and CM proliferation following myocardial ischemia in rats, leading to improved cardiac function.