VEGF165 and angiopoietin-1 decreased myocardium infarct size through phosphatidylinositol-3 kinase and Bcl-2 pathways.
Angiogenic growth factors, vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) could decrease myocardial infarct size, which was assumed to be related with newly formed capillaries. We doubted that these capillaries could do this solely and the potential protective mechanisms of VEGF and Ang1 on myocardium need to be evaluated. Three types of adenoviruses encoding human VEGF(165) (Ad-VEGF(165)), human angiopoietin-1 (Ad-Ang1) and green fluorescent protein (Ad-GFP, as a parallel control) were constructed. Experiments were taken both in vitro and in vivo. As in vitro, the antiapoptosis effect of VEGF(165), Ang1 and VEGF(165)+Ang1 on cardiac myoblasts was observed, which seemed to be related with the activation of phosphatidylinositol-3 kinase and Bcl-2 pathways. As in vivo, adenoviruses were intramyocardially injected immediately after the ligation of the left anterior descending coronay arteries in rats. The results showed positive effect of VEGF(165), Ang1 and VEGF(165)+Ang1 on decreasing the myocardial infarct size at the 7th day. Myocardial PI-3K activity and Bcl-2 expression were elevated relatively at the 3rd day. The protective effect of VEGF(165) and Ang1 on the myocardium may broaden their functional research and contribute to their clinical use in the future.
Zhou
L
L
Department of Cardiology, the first affiliated hospital, Nanjing Medical University, Nanjing, China.
Ma
W
W
Yang
Z
Z
Zhang
F
F
Lu
L
L
Ding
Z
Z
Ding
B
B
Ha
T
T
Gao
X
X
Li
C
C
D000256:Adenoviridae / Q000235:genetics; D042501:Angiogenic Proteins / Q000235:genetics*; D042683:Angiopoietin-1 / Q000235:genetics; D000818:Animals; D042783:Endothelial Cells; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014161:Transduction, Genetic / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D042501:Angiogenic Proteins; D042683:Angiopoietin-1; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases