title: Hepatocyte growth factor, but not vascular endothelial growth factor, attenuates angiotensin II-induced endothelial progenitor cell senescence.
abstract: 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.
authors.affiliation: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 565-0871, Osaka, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sanada
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Taniyama
authors.forename: Junya
authors.initials: J
authors.lastname: Azuma
authors.forename: Kazuma
authors.initials: K
authors.lastname: Iekushi
authors.forename: Norio
authors.initials: N
authors.lastname: Dosaka
authors.forename: Toyohiko
authors.initials: T
authors.lastname: Yokoi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Koibuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kusunoki
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: 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
chemical_list: 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