[Combined gene therapy enhances collateral vascularization in coronary artery occlusion swine model].
OBJECTIVE
To investigate the efficacy of combined gene transfer of vascular endothelial growth factor (VEGF) and angiotensin-1 (Ang-1) in swine coronary artery occlusion.


METHODS
Swine underwent left thoracotomy followed by ligation of left anterior descending coronary artery. Constructed PCD(2)/VEGF and/or PCD(2)/Ang-1 eukaryotic expression plasmid was directly injected into the swine myocardium. RT-PCR, immunohistochemistry, capillary density and arteriole density were used to detect gene expression and biological effect. Coronary angiography was done to evaluate collateral circulation of the occluded artery.


RESULTS
High levels of VEGF and Ang-1 mRNA and protein expression were detected. There was a significant increase in the number of capillaries and arterioles as compared with a control group (P < 0.05). Capillary density and arteriole density of the combination therapy group were higher than those of the swing receiving either therapy alone. Coronary angiography showed better collateral circulation in the combination therapy group.


CONCLUSIONS
Direct injection of PCD(2)/VEGF and PCD(2)/Ang-1 can transfect the myocardium and express VEGF and Ang-1 protein. Combined gene transfer of VEGF and Ang-1 can increase capillary and arteriole number and enhance collateral circulation of the occluded coronary artery more effectively.
Zu
Ling-yun
LY
Department of Cardiology, Peking University Third Hospital, Beijing 100034, China.
Jiang
Jie
J
Yang
Yang
Y
Chen
Ming
M
Chen
Li
L
Yu
Zhuo
Z
Gao
Wei
W
D000803:Angiotensin I / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D013552:Swine; D013556:Swine, Miniature; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000803:Angiotensin I