Modulation of growth factor gene expression in vascular cells by oxidative stress.

Reactive oxygen species (ROS) generated in and around vascular endothelium may play a role in normal cellular signaling mechanisms but may also be an important causative factor in endothelial dysfunction underlying the development of atherosclerosis, diabetes complications, and ischemia-reperfusion injury. ROS influence a variety of molecular and cellular activities, including changes in the cellular localization of regulatory factors, protein modification, and altered gene expression, which in turn influence cellular phenotype. One mechanism by which ROS exert their cellular effects involves their ability to modulate the expression and function of vascular genes, such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF), which play key atherogenic roles by their regulation of cell growth, differentiation, and fibroproliferative responsiveness. In this review the authors describe the changes induced by oxidative stress on the profile of growth factor gene expression in endothelial cells, and the impact these modifications have on endothelial phenotype as well as on the behavior of neighboring vascular smooth muscle cells and fibroblasts. The authors also discuss the involvement of redox-sensitive transcription factors in these regulatory processes.