Stable Compounds of Cigarette Smoke Induce Endothelial Superoxide Anion Production via NADPH Oxidase Activation

Jaimes, Edgar A.; DeMaster, Eugene G.; Tian, Run Xia; Raij, Leopoldo

doi:10.1161/01.atv.0000127083.88549.58

Cited by 227 publications

(177 citation statements)

References 38 publications

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“…These findings are consistent with previous findings indicating that cigarette smoke induces endothelial superoxide anion production via NADPH oxidase activation. 29 Therefore, our results demonstrate the …”

Section: Discussionsupporting

confidence: 66%

Nox2-Containing NADPH Oxidase Deficiency Confers Protection From Hindlimb Ischemia in Conditions of Increased Oxidative Stress

Haddad

Dussault

Groleau

et al. 2009

ATVB

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Objective-Because Nox2-containing NADPH oxidase is a major source of ROS in the vasculature, we investigated its potential role for the modulation of ischemia-induced neovascularization in conditions of increased oxidative stress. Methods and Results-To mimic a clinical situation of increased oxidative stress, mice were exposed to cigarette smoke before and after the surgical induction of hindlimb ischemia. Nox2 expression and oxidative stress in ischemic tissues were significantly increased in wild-type mice, but not in mice deficient for the Nox2-containing NADPH oxidase (Nox2 Ϫ/Ϫ ). Nox2 Ϫ/Ϫ mice demonstrated faster blood flow recovery, increased capillary density in ischemic muscles, and improved endothelial progenitor cell functional activities compared to Nox2 ϩ/ϩ mice. In addition, Nox2 deficiency was associated with increased antioxidant and nitrite concentrations in plasma, together with a preserved expression of eNOS in ischemic tissues. In vitro, Nox2Ϫ/Ϫ endothelial cells exhibit resistance against superoxide induction and improved VEGF-dependent angiogenic activities compared to Nox2 ϩ/ϩ endothelial cells. Importantly, the beneficial effects of Nox2 deficiency on neovascularization in vitro and in vivo were lost after treatment with the NO inhibitor L-NAME. Conclusions-Nox2-containing NADPH oxidase deficiency protects against ischemia in conditions of increased oxidative stress. The mechanism involves improved neovascularization through a reduction of ROS formation, preserved activation of the VEGF/NO angiogenic pathway, and improved functional activities of endothelial progenitor cells.

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Section: Discussionsupporting

confidence: 66%

Nox2-Containing NADPH Oxidase Deficiency Confers Protection From Hindlimb Ischemia in Conditions of Increased Oxidative Stress

Haddad

Dussault

Groleau

et al. 2009

ATVB

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“…8,9 Once active NADPH oxidase forms, it catalyzes the transfer of electrons from NADPH to molecular oxygen producing the superoxide anion (O 2 NADPH oxidase is the main cellular source of ROS in mononuclear and granulocytic leukocytes and is involved in host defense. 9 It has been shown that CS induces endothelial O 2 ⅐Ϫ production via NADPH oxidase activation in cell culture systems, 11,12 which was associated with CS-induced lung inflammation and injury. Recent studies have shown that NADPH oxidase subunits are under tight regulatory control in physiological conditions.…”

Section: Cigarette Smoke (Cs) Induces Recruitment Of Inflammatory Celmentioning

confidence: 99%

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Yao

Edirisinghe

Yang

et al. 2008

The American Journal of Pathology

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Cigarette smoke (CS) induces recruitment of inflammatory cells in the lungs leading to the generation of reactive oxygen species (ROS), which are involved in lung inflammation and injury. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a multimeric system that is responsible for ROS production in mammalian cells. We hypothesized that NADPH oxidase-derived ROS play an important role in lung inflammation and injury and that targeted ablation of components of NADPH oxidase (p47 phox and gp91 phox ) would protect lungs against the detrimental effects of CS. To test this hypothesis, we exposed p47 phox؊/؊ and gp91 phox؊/؊ mice to CS and examined inflammatory response and injury in the lung. Surprisingly, although CS-induced ROS production was decreased in the lungs of p47 phox؊/؊ and gp91 phox؊/؊ mice compared with wild-type mice, the inflammatory response was significantly increased and was accompanied by development of distal airspace enlargement and alveolar destruction. This pathological abnormality was associated with enhanced activation of the TLR4-nuclear factor-B pathway in response to CS exposure in p47 phox؊/؊ and gp91 phox؊/؊ mice. This phenomenon was confirmed by in vitro studies in which treatment of peritoneal macrophages with a nuclear factor-B inhibitor reversed the CS-induced release of proinflammatory mediators. Thus, these data suggest that genetic ablation of components of NADPH oxidase enhances susceptibility to the proinflammatory effects of CS leading to airspace enlargement and alveolar damage.

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“…N G -nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NOS at the haem site (Pritchard et al 1995;Munzel et al 2000;Pritchard et al 2001;Stepp et al 2002) and apocynin, an inhibitor of NADPH oxidase protein complex formation (Jaimes et al 2004), were obtained from Sigma and utilized in inhibition studies.…”

Section: Additional Reagents and Materialsmentioning

confidence: 99%

“…The combined effects of NOS and NADPH oxidase in H 2 O 2 -induced increases in intracellular O 2 .-in PAEC were investigated using L-NAME, which blocks both NO and O 2 .-production by NOS (Pritchard et al 1995;Munzel et al 2000;Pritchard et al 2001) and apocynin, a pharmacological inhibitor of NADPH oxidase (Jaimes et al 2004). …”

Section: Nos and Nadph Oxidase Co-inhibitionmentioning

confidence: 99%

Mechanisms of H2O2-induced oxidative stress in endothelial cells

Coyle

Martínez

Coleman

et al. 2006

Free Radical Biology and Medicine

131

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Stable Compounds of Cigarette Smoke Induce Endothelial Superoxide Anion Production via NADPH Oxidase Activation

Cited by 227 publications

References 38 publications

Nox2-Containing NADPH Oxidase Deficiency Confers Protection From Hindlimb Ischemia in Conditions of Increased Oxidative Stress

Nox2-Containing NADPH Oxidase Deficiency Confers Protection From Hindlimb Ischemia in Conditions of Increased Oxidative Stress

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

Mechanisms of H2O2-induced oxidative stress in endothelial cells

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