Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart.
Vascular endothelial growth factor (VEGF) is a key angiogenic factor and has been used experimentally for induction of neovasculature in ischemic myocardium. However, blood vessels induced by VEGF are immature. Angiopoietin-1 (ang-1) has the ability to recruit and sustain periendothelial support cells and promote vascular maturation. Thus, co-expression of the two may yield a better result than expression of either one alone. Two adeno-associated viral vectors (AAV), CMVVEGF and CMVang-1 with the CMV promoter driving VEGF or ang-1 gene expression, respectively, were injected into ischemic mouse hearts individually or together in different ratios. The results show that co-injected groups had more capillaries than the CMVang-1 group and similar densities of capillaries and alpha-actin positive vessels as the CMVVEGF group. Neovasculature induced by CMVVEGF was leaky. In contrast, neovasculature in CMVang-1-injected or CMVVEGF and CMVang-1 co-injected hearts was less leaky than that in CMVVEGF-injected hearts. The group that received CMVang-1 and CMVVEGF in a 1:1 ratio had the smallest infarct size and best cardiac function and regional wall movement among all the groups. We conclude that ang-1 and VEGF can compensate for each others' shortcomings and yield a better therapeutic effect by acting together.
Su
Hua
H
Department of Medicine, University of California, San Francisco, San Francisco, CA 94143-0793, USA. hua.su@ucsf.edu
Takagawa
Junya
J
Huang
Yu
Y
Arakawa-Hoyt
Janice
J
Pons
Jennifer
J
Grossman
William
W
Kan
Yuet Wai
YW
D042683:Angiopoietin-1 / Q000096:biosynthesis*; D000818:Animals; D000229:Dependovirus; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009203:Myocardial Infarction / Q000378:metabolism* / Q000628:therapy*; D017202:Myocardial Ischemia / Q000628:therapy*; D018919:Neovascularization, Physiologic; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D042683:Angiopoietin-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A