Regulation of Vascular Endothelial Growth Factor Transcripts by Hydrogen Peroxide in Rat Heart Endothelial Cells

The aim of this series of experiments was to study the mechanism of increased vascular permeability in response to hydrogen peroxide (H2O2). Addition of H2O2 stimulated vascular endothelial growth factor (VEGF) gene expression in rat heart endothelial cells in a dose and time-dependent manner. VEGF transcripts reached the highest level by 2 h and decayed after 5 h with 0.5 mM H2O2. Addition of cycloheximide superinduced and actinomycin D abolished the induction. The induction could be blocked by protein kinase C inhibitors, H7 and GF109203X. These results suggest that induction of VEGF transcripts by H2O2 is mediated by protein kinase C pathway and is dependent on de novo RNA synthesis. Our data suggests that H2O2 plays a role in angiogenesis by promoting the production of VEGF