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

FEBS Letters

Savi, Pierre¹  Bono, Fran¢oise¹  Herbert, Jean-Marc¹ 

[1]Haemobiology Research Department, Sanofi Recherche, 195 Route d'Espagne, 31036 Toulouse, France

关键词: Smooth muscle cell;    Proliferation;    Hydrogen peroxide;    H2O2;    Basic fibroblast growth factor;   

DOI  :  10.1016/0014-5793(96)00998-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Increased generation of active oxygen species such as hydrogen peroxide (H₂O₂) may be important in vascular smooth muscle cell growth associated with atherosclerosis and restenosis. In this work, we showed that H₂O₂ 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 μM 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 H₂O₂. H₂O₂-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. H₂O₂ strongly increased the affinity of bFGF for its receptor-1 at the surface of the SMC, therefore showing that the mitogenic effect of H₂O₂ might occur through a direct effect on the bFGF receptor.

【 授权许可】

Unknown