Hepatocyte growth factor, but not vascular endothelial growth factor, attenuates angiotensin II-induced endothelial progenitor cell senescence.
Although both hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) are potent angiogenic growth factors in animal models of ischemia, their characteristics are not the same in animal experiments and clinical trials. To elucidate the discrepancy between HGF and VEGF, we compared the effects of HGF and VEGF on endothelial progenitor cells under angiotensin II stimulation, which is a well-known risk factor for atherosclerosis. Here, we demonstrated that HGF, but not VEGF, attenuated angiotensin II-induced senescence of endothelial progenitor cells through a reduction of oxidative stress by inhibition of the phosphatidylinositol-3,4,5-triphosphate/rac1 pathway. Potent induction of neovascularization of endothelial progenitor cells by HGF, but not VEGF, under angiotensin II was also confirmed by in vivo experiments using several models, including HGF transgenic mice.
Sanada
Fumihiro
F
Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 565-0871, Osaka, Japan.
Taniyama
Yoshiaki
Y
Azuma
Junya
J
Iekushi
Kazuma
K
Dosaka
Norio
N
Yokoi
Toyohiko
T
Koibuchi
Nobutaka
N
Kusunoki
Hiroshi
H
Aizawa
Yoshifusa
Y
Morishita
Ryuichi
R
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D018129:Phosphatidylinositol Phosphates; D042461:Vascular Endothelial Growth Factor A; D014662:Vasoconstrictor Agents; C060974:phosphatidylinositol 3,4,5-triphosphate; D000804:Angiotensin II; D017228:Hepatocyte Growth Factor; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein