Object—Platelet isoprostane 8-iso-PGF2 , a proaggregating molecule, is believed to derive from nonenzymatic oxidation of arachidonic acid. We hypothesized that NADPH is implicated in isoprostane formation and platelet activation. Methods and Results—We studied 8-iso-PGF2 in platelets from 8 male patients with hereditary deficiency of gp91, the catalytic subunit of NADPH oxidase, and 8 male cont...

BACKGROUND Angiotensin II induces both cardiac and vascular smooth muscle (VSM) hypertrophy. Recent studies suggest a central role for a phagocyte-type NADPH oxidase in angiotensin II-induced VSM hypertrophy. The possible involvement of an NADPH oxidase in the development of cardiac hypertrophy has not been studied. Methods and Results- Mice with targeted disruption of the NADPH oxidase subunit...

Background—NADPH oxidase is believed to modulate arterial tone, but its role in humans is still unclear. The objective of this study was to evaluate whether NADPH oxidase is involved in flow-mediated arterial dilation (FMD). Methods and Results—Twenty-five patients with hereditary deficiency of gp91, the catalytic core of NADPH oxidase, (X-CGD), 25 healthy subjects, and 25 obese patients matche...

OBJECTIVE The inhibition of oxidative stress is among the most relevant pleiotropic effects of statins. The mechanism by which statins exert their antioxidant effect in vivo is still undefined. NADPH oxidase is among the most important sources of reactive oxygen species involved in atherosclerotic disease. Methods/Results- We developed an ELISA to evaluate serum levels of soluble-gp91(phox), th...

BACKGROUND Gp91(phox) is a transmembrane protein and the catalytic core of the NADPH oxidase complex of neutrophils. Lack of this protein causes chronic granulomatous disease (CGD), a rare genetic disorder characterized by severe and recurrent infections due to the incapacity of phagocytes to kill microorganisms. METHODOLOGY Here we optimize a prokaryotic cell-free expression system to produc...

Chronic granulomatous disease (CGD) is an inherited deficiency of the superoxide-generating phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, resulting in recurrent, severe bacterial and fungal infections. The X-linked form of this disorder (X-CGD) results from mutations in the X-linked gene for gp91(phox), the larger subunit of the oxidase flavocytochrome b(558). In this s...

Alcoholic cardiomyopathy (ACM) resulting from excess alcohol consumption is an important cause of heart failure (HF). Although it is assumed that the cardiotoxicity of the ethanol (EtOH)-metabolite acetaldehyde (ACA) is central for its development and progression, the exact mechanisms remain obscure. Murine cardiomyocytes (CMs) exposed to ACA or EtOH showed increased superoxide (O2(•-)) levels ...

We investigated the effects of dexamethasone or indomethacin on the NADPH oxidase activity, cytochrome b558 content, and expression of genes encoding the components gp91-phox and p47-phox of the NADPH oxidase system in the human monocytic THP-1 cell line, differentiated with IFN-gamma and TNF-alpha, alone or in combination, for up to 7 days. IFN-gamma and TNF-alpha, alone or in combination, cau...

RATIONALE The role of NADPH oxidase activation in pneumonia is complex because reactive oxygen species contribute to both microbial killing and regulation of the acute pulmonary infiltrate. The relative importance of each role remains poorly defined in community-acquired pneumonia. OBJECTIVES We evaluated the contribution of NADPH oxidase-derived reactive oxygen species to the pathogenesis of...

Blood flow throughout the vascular circuit exerts a tangential force called shear stress upon all vessel walls. Under homeostatic conditions, shear stress is maintained within a narrow range. It has been shown that an alteration from this normal range of shear stress activates a biochemical signaling cascade in a process termed mechanotransduction. Although the signaling mechanism has not been ...