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(Circulation Research. 2005;96:818.)
© 2005 American Heart Association, Inc.

Review

NAD(P)H Oxidase–Dependent Self-Propagation of Hydrogen Peroxide and Vascular Disease

Hua Cai

From the Section of Cardiology, Department of Medicine, The Division of Biological Sciences and Pritzker School of Medicine, The University of Chicago, Ill.

Correspondence to Hua "Linda" Cai, MD, PhD, Section of Cardiology, Department of Medicine, The Division of Biological Sciences and Pritzker School of Medicine, The University of Chicago, 5841 S. Maryland Ave, MC6088, Chicago, IL 60637. E-mail lcai{at}medicine.bsd.uchicago.edu or hcai@medicine.bsd.uchicago.edu

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].

Key Words: reactive oxygen species • hydrogen peroxide (H₂O₂) • endothelial function • vascular NAD(P)H oxidases • Nox • uncoupled endothelial nitric oxide synthase (eNOS) • atherosclerosis

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