Abstract:Aim To investigate the effect of human vascular endothelial growth factor 165 (hVEGF165) cDNA mediated by recombinant adeno-associated viral vector2 (rAAV-2) on the angiogenesis in ischemic myocardium. Methods Rabbit myocardial ischemic models were generated by ligation of the anterior descending coronary artery. All these models were randomly divided into 4 groups: VEGF high dose group (10 12v.g./kg), VEGF middle dose group (10 11v.g./kg), VEGF low dose group (10 10v.g./kg) and control group. RAAV-2/hVEGF165 or PBS was injected into the ischemic myocardium respectively. After 4 weeks, the expression of objective gene was evaluated by RT-PCR and ELISA. The histological changes of myocardium were observed through histological sections. Myocardial capillary counts were calculated to evaluate the proangiogenic effects. Results With the increasing dosage of injected rAAV-2/hVEGF165, hVEGF165/GAPDH mRNA ratio were 0.14±0.03, 0.40±0.04 and 0.64±0.04 respectively, while VEGF protein content were 64.6±8.0 ng/L, 327.1±9.9 ng/L and 471.6±6.9 ng/L respectively. The changes of expression were dose-dependent and there were significant difference among the groups(p<0.01). In rAAV-2/hVEGF165 10 10, 10 11 and 10 12 v.g./kg treatmented groups, the microvessel counts were (4.6±1.3)/HPF, (11.6±1.8)/HPF and (21.8±3.1)/HPF respectively, while (4.5±1.5)/HPF in control group. There was significant difference between the 10 11, 10 12 v.g./kg hVEGF165 gene-treated groups and control group(both p<0.01), but no such difference between 10 10 v.g./kg hVEGF165 gene-treated group and control group(p>0.05). The result of correlation analysis showed the microvessel counts were related with the dosages of rAAV-2/hVEGF165 positively (r=0.910,p<0.01). Conclusions hVEGF165 gene mediated by rAAV-2 can be efficiently transferred into rabbit ischemic heart and induce angiogenesis of myocard-