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


CONCLUSIONS
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.
Liu
Xiang
X
The First Affiliate Hospital of Nanjing Medical University, Nanjing, P. R. China.
Chen
Yijiang
Y
Zhang
Fumin
F
Chen
Lizhen
L
Ha
Tuanzhu
T
Gao
Xiang
X
Li
Chuanfu
C
D000256:Adenoviridae; D042683:Angiopoietin-1 / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D015153:Blotting, Western; D015316:Genetic Therapy; D006321:Heart / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology* / Q000627:therapeutic use
D042683:Angiopoietin-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A