Intramyocardial injection of vascular endothelial growth factor gene improves cardiac performance and inhibits cardiomyocyte apoptosis.
BACKGROUND
Previous studies suggest that vascular endothelial growth factor (VEGF) is a regulator of naturally occurring angiogenesis. However, whether VEGF plays a role in cardiomyocyte apoptosis is not known.


OBJECTIVE
To investigate the effects of intramyocardial injection of VEGF165 cDNA on cardiac performance and cardiomyocyte apoptosis in a rat model of acute myocardial infarction.


METHODS
Forty male Sprague-Dawley rats underwent left coronary artery ligation and were randomised to receive VEGF165 cDNA (treated group) or pcDNA3.1 (control), injected directly into the border zone of the ischaemic myocardium. Twenty rats underwent thoracotomy and injection of pcDNA3.1, without coronary ligation (sham group). Haemodynamic and apoptotic parameters were measured two weeks after injection.


RESULTS
Three sham, eight control, and five treated animals died. Haemodynamic parameters and microvessel counts in the treated group were significantly better than in the control (P<0.05 to 0.01). Apoptotic index in the treated group was less than in the control (P<0.01). Caspase-3 activation and mitochondrial cytochrome c release in the treated group were also lower than in the control (P<0.01). VEGF165 cDNA treatment significantly inhibited p53, Fas, Bax, and increased VEGF and Bcl-2 expression in the myocardium.


CONCLUSIONS
Intramyocardial injection of VEGF165 cDNA significantly improved cardiac performance, stimulated angiogenesis and reduced cardiomyocyte apoptosis, in a rat model of acute myocardial infarction.
Ruixing
Yin
Y
Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China. yinruixing@yahoo.com.cn
Dezhai
Yang
Y
Hai
Wu
W
Kai
Huang
H
Xianghong
Wu
W
Yuming
Chen
C
D000818:Animals; D017209:Apoptosis; D018076:DNA, Complementary; D015870:Gene Expression; D015316:Genetic Therapy; D006333:Heart Failure / Q000209:etiology* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D032342:Muscle Cells; D009203:Myocardial Infarction; D017202:Myocardial Ischemia; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D018076:DNA, Complementary; D042461:Vascular Endothelial Growth Factor A