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The mitogenic effect of H 2 O 2 for vascular smooth muscle cells is mediated by an increase of the affinity of basic fibroblast growth factor for its receptor
Author(s) -
Herbert Jean-Marc,
Bono Fran¢oise,
Savi Pierre
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00998-2
Subject(s) - basic fibroblast growth factor , deferoxamine , vascular smooth muscle , catalase , receptor , cell growth , biology , growth factor , fibroblast growth factor , endocrinology , chemistry , medicine , microbiology and biotechnology , biochemistry , oxidative stress , smooth muscle
Increased generation of active oxygen species such as hydrogen peroxide (H 2 O 2 ) may be important in vascular smooth muscle cell growth associated with atherosclerosis and restenosis. In this work, we showed that H 2 O 2 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 H 2 O 2 . H 2 O 2 ‐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. H 2 O 2 strongly increased the affinity of bFGF for its receptor‐1 at the surface of the SMC, therefore showing that the mitogenic effect of H 2 O 2 might occur through a direct effect on the bFGF receptor.