Therapeutic angiogenesis with the use of vascular endothelial growth factor 165 gene in the myocardium of miniature swine

The purpose of the present study was to examine whether adenovirus-mediated vascular endothelial growth factor l65 (VEGFl65) can enhance collateral vessel formation of coronary artery and improve regional myocardial perfusion and function. Using a miniature swine model of chronic myocardial ischemia, the replication-deficient recombinant adenovirus vector containing complementary deoxyribonucleic acid (cDNA) for human VEGFl65 (Ad-VEGFl65) or for beta-galactosidase (Ad-Gal) was administered directly into the ischemic myocardium in the left circumflex (LCX) distribution. Myocardial perfusion and function were assessed by electrocardiogram-gated single photon emission computed tomography (SPECT) imaging and collateral vessel development of coronary artery was assessed by ex vivo coronary angiography (CAG). Four weeks after Ad-VEGF165 administration, SPECT imaging demonstrated a significant reduction in ischemic area (P<0.01) and ischemic severity (P<0.01), and a substantial improvement in left ventricular ejection fraction (P<0.01) and regional wall motion in the LCX distribution (P<0.05), as compared with that of control animals and that before administration of Ad-VEGFl65. Collateral vessel development with Rentrop Grading was also significantly greater in Ad-VEGF165 animals than in the Ad-Gal control animals (P<0.05). It's concluded that Ad-VEGFl65 can induce collateral vessel development in ischemic myocardium and result in significant improvement in myocardial perfusion and function.