Vascular NADPH oxidases: molecular mechanisms of activation

Oxygen-derived free radicals are thought to contribute to the initiation and progression of cardiovascular disease via several different mechanisms, such as consumption of nitric oxide, oxidation of proteins and lipids, and activation of redox-sensitive signalling cascades. Vascular NADPH oxidases are important sources of vascular radical formation. The activities of these enzymes, which in some aspects are similar to the leukocyte NADPH oxidase, are controlled on the expression level and complex activation mechanisms. As a plethora of vascular stimuli, such as growth factors, cytokines, physical stimuli, and lipids elicits radical formation by these enzymes, a careful analysis is required for the understanding of the activation of the NADPH oxidases. This article reviews the components of the NADPH oxidases in leukocytes and vascular tissue. Emphasis is put on the activation of the oxidases, including upstream signalling events and molecular modes of interaction between the subunits.