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

Abstract

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.