The mitogenic effect of H2O2 for vascular smooth muscle cells is mediated by an increase of the affinity of basic fibroblast growth factor for its receptor.
Increased generation of active oxygen species such as hydrogen peroxide (H202) may be important in vascular smooth muscle cell growth associated with atherosclerosis and restenosis. In this work, we showed that H202 was a potent mitogen for growth-arrested cultured human aortic smooth muscle cells (SMC), stimulating an increase in cell number at 10 nM to 100 microM concentration. This effect was inhibited in a dose-dependent manner by catalase, deferoxamine, dimethylthiourea or probucol showing that it was dependent on the oxidative activity of H202. H202-induced SMC proliferation was strongly and specifically inhibited by a neutralizing monoclonal antibody directed against basic fibroblast growth factor (bFGF) but was not due to increased expression of bFGF or the bFGF receptor-1 (FGFR-1) by SMC. H202 strongly increased the affinity of bFGF for its receptor-1 at the surface of the SMC, therefore showing that the mitogenic effect of H202 might occur through a direct effect on the bFGF receptor.
Herbert
J M
JM
Haemobiology Research Department, Sanofi Recherche, Toulouse, France. jean-marc.herbert@tls1.elfsanofi.fr
Bono
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Savi
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D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta; D002374:Catalase / Q000494:pharmacology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010084:Oxidation-Reduction; D011341:Probucol / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D000975:Antioxidants; D007502:Iron Chelating Agents; D008934:Mitogens; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; C038983:1,3-dimethylthiourea; D006861:Hydrogen Peroxide; D002374:Catalase; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D013890:Thiourea; D003676:Deferoxamine; D011341:Probucol