NAD(P)H oxidase-dependent self-propagation of hydrogen peroxide and vascular disease.
Excessive production of reactive oxygen species in the vasculature contributes to cardiovascular pathogenesis. Among biologically relevant and abundant reactive oxygen species, superoxide (O2*-) and hydrogen peroxide (H2O2) appear most important in redox signaling. Whereas O2*- predominantly induces endothelial dysfunction by rapidly inactivating nitric oxide (NO*), H2O2 influences different aspects of endothelial cell function via complex mechanisms. This review discusses recent advances establishing a critical role of H2O2 in the development of vascular disease, in particular, atherosclerosis, and mechanisms whereby vascular NAD(P)H oxidase-derived H2O2 amplifies its own production. Recent studies have shown that H2O2 stimulates reactive oxygen species production via enhanced intracellular iron uptake, mitochondrial damage, and sources of vascular NAD(P)H oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase (eNOS). This self-propagating phenomenon likely prolongs H2O2-dependent pathological signaling in vascular cells, thus contributing to vascular disease development. The latest progress on Nox functions in vascular cells is also discussed [Nox for NAD(P)H oxidases, representing a family of novel NAD(P)H oxidases].
Cai
Hua
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Section of Cardiology, Department of Medicine, The Division of Biological Sciences and Pritzker School of Medicine, The University of Chicago, Ill 60637, USA. lcai@medicine.bsd.uchicago.edu
D001161:Arteriosclerosis / Q000209:etiology*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D020935:MAP Kinase Signaling System; D019255:NADPH Oxidases / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D052250:Nitric Oxide Synthase Type III; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014652:Vascular Diseases / Q000209:etiology*
D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D019255:NADPH Oxidases