title: Hepatocyte growth factor stimulated angiogenesis without inflammation: differential actions between hepatocyte growth factor, vascular endothelial growth factor and basic fibroblast growth factor.
abstract: Based on the potent angiogenic effects of hepatocyte growth factor (HGF), therapeutic angiogenesis using human HGF plasmid DNA increased tissue perfusion and reduced symptoms in patients with critical limb ischemia (CLI) in randomized placebo-controlled clinical trials. To explore further the potent angiogenic activity of HGF, the present study compared the effects of HGF, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) on angiogenesis and vascular inflammation. All of HGF, VEGF and bFGF significantly induced the formation of capillary blood vessel and granulation tissue in the rat paper disc model as an in vivo animal model of angiogenesis. However, although HGF, bFGF and VEGF significantly increased the growth of vascular endothelial cells, bFGF alone, but not HGF or VEGF, significantly increased the growth of vascular smooth muscle cells (VSMCs) in the in vitro proliferation assay. In addition, bFGF, but not HGF or VEGF, significantly activated an essential transcription factor for inflammation, NFκB, and gene expression of its downstream inflammation-related cytokines (IL-8 and MCP-1) in VSMCs, accompanied by an increase in the vascular permeability in the rat paper disc model. Thus, the present results indicated that HGF induced angiogenesis without vascular inflammation, different from bFGF and VEGF. These different properties between HGF, VEGF and bFGF might affect the efficiency of therapeutic angiogenesis.
authors.affiliation: AnGes MG, Inc., Osaka, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kaga
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kawano
authors.forename: Makoto
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Taniyama
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D043925:Angiogenesis Inducing Agents; D018932:Chemokine CCL2; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D016209:Interleukin-8; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000097782:NF-kappaB-Inducing Kinase; C491766:Ccl2 protein, rat