Combination of angiopoietin-1 and vascular endothelial growth factor gene therapy enhances arteriogenesis in the ischemic myocardium.
We hypothesised that angiopoietin-1 (Ang-1), in conjunction with vascular endothelial growth factor (VEGF) gene therapy, can enhance arteriogenesis and angiogenesis during myocardial ischemia. Mice were given a single intramyocardial injection of saline, phVEGF-A(165) and phAng-1 or a combination thereof into the non-ischemic normal heart or into the ischemic border zone of the infarcted heart. In the normal and the ischemic myocardium, gene transfer of phVEGF-A(165) alone increased the myocardial capillary density by 16% and 36%, respectively, and phAng-1 had a similar effect. In the normal heart, the ratio of arteriolar to capillary densities increased with phVEGF-A(165) and more so in the ischemic myocardium where phAng-1 also had an effect. Furthermore, the combination of plasmids induced an up to 7.5-fold increase. Transient overexpression of VEGF-A(165) boosts endogenous arteriogenesis in addition to capillary angiogenesis. Ang-1 further boosts this effect at the arteriolar level.
Siddiqui
A J
AJ
Department of Cardiology, Karolinska Institute, Stockholm, Sweden. Anwar.J.Siddiqui@medhs.ki.se
Blomberg
P
P
Wärdell
E
E
Hellgren
I
I
Eskandarpour
M
M
Islam
K B
KB
Sylvén
C
C
D042683:Angiopoietin-1 / Q000235:genetics*; D000818:Animals; D019556:COS Cells; D002196:Capillaries / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction; D017202:Myocardial Ischemia; D018919:Neovascularization, Physiologic; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
D042683:Angiopoietin-1; D042461:Vascular Endothelial Growth Factor A