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 (O-2(center dot-)) and hydrogen peroxide ( H2O2) appear most important in redox signaling. Whereas O-2(center dot-) predominantly induces endothelial dysfunction by rapidly inactivating nitric oxide (NO center dot), 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].