NADPH oxidase and endothelial cell function

Abstract

Intracellular ROS (reactive oxygen species) such as superoxide and H2O2 have been increasingly appreciated to have a role in endothelial pathophysiology. Of the several sources within the vasculature, a family of multi-subunit NADPH oxidases appears to be a predominant contributor of endothelial superoxide. More importantly, this enzyme system is activated by numerous stimuli and is involved in triggering diverse intracellular signalling pathways (‘redox-sensitive’ signalling pathways) that have a central role in conditions such as endothelial activation and inflammation, cell growth, apoptosis and hypertrophy. Furthermore, NADPH oxidase-derived superoxide contributes to the impairment of endothelium-dependent vasodilatation by inactivating nitric oxide; the resultant endothelial dysfunction is implicated in the pathophysiology of diseases such as atherosclerosis, hypertension, diabetic vasculopathy and heart failure. A detailed understanding of the regulation of NADPH oxidases and their modulation and downstream effects may define novel therapeutic targets for cardiovascular disease prevention and treatment in the clinical setting, in contrast with global antioxidant therapy which has to date been disappointing.