Vascular Endothelial Growth Factor Vegf <sub> 165 </ Sub>, Of Angiopoietin-1 On Myocardial Protective Effect Of,

Biological bypass, an angiogenic therapeutic method arised from the last decade, is an innovative remedy for the ischemic heart and peripheral vascular diseases. This method is to induce new vessel formation in the ischemic region by delivering angiogenic growth factors or their expressing vectors to the affected part and therefore to ameliorate blood perfusion. In 1996 and 1998, Isner group successfully introduced naked plasmid vector expressing human vascular endothelial growth factor 165 (VEGF165) into patient with ischemic hindlimb or heart and got satisfactory outcomes. In 1999, Rosengart TK, et al. also demonstrated the efficiency of biological bypass for the therapy of patient with coronary heart disease by intramyocardial administration of adenoviral vector encoding for human vascular endothelial growth factor 121 (VEGF121). In China, therapeutic plasmid expressing human VEGF165 will be recently applied in Phase I clinical trial.The present research is to establish the technical platform of biological bypass, and to explore the function of angiogenic growth factors on angiogenesis and cardiac protection. For this purpose, cDNAs of humanVEGF165 and angiopoietin-1 (Angl), were cloned by RT-PCR. Replication-deficient adenoviral vector encoding for human VEGF165 (Ad-VEGF165) or Angl (Ad-Angl) was constructed by homologous recombination. The protective effects of VEGF165 and Angl on myocardiumwere then investigated in vitro and in vivo. In H9C2 cardiac myoblasts, VEGF165 and Angl can protect cells from apoptosis induced by H2O2. While in a rat left anterior descending coronary ligation model, VEGFi65 and Angl can decrease the myocardial infarct area. Both protective properties of VEGF165 and Angl in vivo and in vitro are contributed partially to the activiation of phosphatidylinositol-3 kinase (PI-3 K) and the up-regulation of anti-apoptotic factor Bcl-2. Our results suggest that VEGFi65 and Angl can be served as candidates for the therapy of ischemic injury of heart.