Myocardial angiogenesis after plasmid or adenoviral VEGF-A165 gene transfer in rat myocardial infarction model

OBJECTIVE: To compare gene transfer of plasmid (P) and adenovirus (Ad) encoding human vascular endothelial growth factor-A165 (hVEGF-A165) angiogenic efficacy and adverse effects as regards apoptosis and ectopic expression of the transgene in a rat myocardial infarction model. METHODS: Myocardial infarction was provoked in Fisher rats. One week later, PhVEGF-A165, PLacZ, AdhVEGF-A165, or AdLacZ was transferred intramyocardially along the border of the myocardial infarction. hVEGF-A expression was detected with ELISA. Myocardial vessel density was analyzed 1 and 4 weeks after gene transfer. Apoptosis was detected by TUNEL staining. Cardiac function was assessed with Tissue Doppler Velocity Imaging. RESULTS: Although AdhVEGF-A165 had substantially higher myocardial hVEGF-A expression than PhVEGF-A165, AdhVEGF-A165 and PhVEGF-A165 induced angiogenic effects to a similar extent with maintained increased arteriolar density after 4 weeks of gene transfer (p < 0.05). The two treatments also improved left ventricular function similarly. Adenoviral gene transfer induced a higher number of TUNEL positive cells than plasmid (p < 0.02). Ectopic expression of the transgene was present with both vectors but substantially higher after adenoviral gene transfer. CONCLUSIONS: AdhVEGF-A165 has no obvious angiogenic advantage over PhVEGF-A165 but more side effects at least in a rat myocardial infarction model. This indicates that PhVEGF-A165 might be more applicable for therapeutic angiogenesis than AdhVEGF-A165.