Modulation of Growth Factor Gene Expression in Vascular Cells by Oxidative Stress

Abstract

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.

Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia–reperfusion injury in rats

“…I/R injury sets up a typical pro-oxidative condition that may be worsened by the diabetic state, which is characterised by increased oxidative stress and reduced anti-oxidative defences [23][24][25]. Enhanced production of reactive oxygen species simulates a hyperoxic state and may lead to HIF-1α ubiquitination and degradation after ischaemia in diabetes [26]. Moreover, hyperglycaemia itself has been shown to inhibit hypoxia-induced stabilisation of HIF-1α protein against degradation [27].…”

Mechanisms of H2O2-induced oxidative stress in endothelial cells

“…Oxidative stress and ROS are also thought to be important in the progression of atherosclerosis, due to their role in endothelial cell gene expression (Eyries et al 2004). This exemplifies the need for continuing study and modeling of cardiovascular disease states, especially as the prevalence continues to rise.…”

High glucose attenuates insulin-induced VEGF expression in bovine retinal microvascular endothelial cells

“…[1][2][3] Both preclinical and clinical studies have shown that VEGF participated in the pathogenesis of proliferative diabetic retinopathy. [4][5][6] Moreover, intraocular VEGF was found increased in the eyes of diabetic patients with blood-retinal barrier breakdown and neovascularization.…”