Regulation of superoxide anion production by NADPH oxidase in monocytes/macrophages: contributions to atherosclerosis.
Monocyte extravasation into the vessel wall has been shown to be a critical step in the development of atherosclerosis. Upon activation, monocytes produce a burst of superoxide anion due to activation of the NADPH oxidase enzyme complex. Monocyte-derived superoxide anion contributes to oxidant stress in inflammatory sites, is required for monocyte-mediated LDL oxidation, and alters basic cell functions such as adhesion and proliferation. We hypothesize that monocyte-derived superoxide anion production contributes to atherosclerotic lesion formation. In this brief review, we summarize our current understanding of the signal transduction pathways regulating NADPH oxidase activation and related superoxide anion production in activated human monocytes. Novel pathways are identified that may serve as future targets for therapeutic intervention in this pathogenic process. The contributions of superoxide anion and NADPH oxidase to atherogenesis are discussed. Future experiments are needed to clarify the exact role of NADPH oxidase-derived superoxide anion in atherogenesis, particularly that derived from monocytes.
Cathcart
Martha K
MK
Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001161:Arteriosclerosis / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D020013:Calcium Signaling; D006801:Humans; D008264:Macrophages / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000201:enzymology / Q000502:physiology*; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D010741:Phospholipases A / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011499:Protein Processing, Post-Translational; D013481:Superoxides / Q000378:metabolism*; D014657:Vasculitis / Q000150:complications / Q000201:enzymology / Q000473:pathology
D013481:Superoxides; D000804:Angiotensin II; D019255:NADPH Oxidases; D011493:Protein Kinase C; D010741:Phospholipases A