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. Aim: To investigate the effects of intramyocardial injection of VEGF(165) 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 VEGF(165) 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). VEGF(165) cDNA treatment significantly inhibited p53, Fas, Bax, and increased VEGF and Bcl-2 expression in the myocardium. Conclusion: Intramyocardial injection of VEGF(165) cDNA significantly improved cardiac performance, stimulated angiogenesis and reduced cardiomyocyte apoptosis, in a rat model of acute myocardial infarction. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.