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The NADPH oxidase Nox4 has anti-atherosclerotic functions

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The NADPH oxidase Nox4 has anti-atherosclerotic functions. / Schürmann, Christoph; Rezende, Flavia; Kruse, Christoph; Yasar, Yakub; Löwe, Oliver; Fork, Christian; Van De Sluis, Bart; Bremer, Rolf; Weissmann, Norbert; Shah, Ajay M.; Jo, Hanjoong; Brandes, Ralf P.; Schröder, Katrin.

In: European Heart Journal, Vol. 36, No. 48, 21.12.2015, p. 3447-3456.

Research output: Contribution to journalArticle

Harvard

Schürmann, C, Rezende, F, Kruse, C, Yasar, Y, Löwe, O, Fork, C, Van De Sluis, B, Bremer, R, Weissmann, N, Shah, AM, Jo, H, Brandes, RP & Schröder, K 2015, 'The NADPH oxidase Nox4 has anti-atherosclerotic functions', European Heart Journal, vol. 36, no. 48, pp. 3447-3456. https://doi.org/10.1093/eurheartj/ehv460

APA

Schürmann, C., Rezende, F., Kruse, C., Yasar, Y., Löwe, O., Fork, C., ... Schröder, K. (2015). The NADPH oxidase Nox4 has anti-atherosclerotic functions. European Heart Journal, 36(48), 3447-3456. https://doi.org/10.1093/eurheartj/ehv460

Vancouver

Schürmann C, Rezende F, Kruse C, Yasar Y, Löwe O, Fork C et al. The NADPH oxidase Nox4 has anti-atherosclerotic functions. European Heart Journal. 2015 Dec 21;36(48):3447-3456. https://doi.org/10.1093/eurheartj/ehv460

Author

Schürmann, Christoph ; Rezende, Flavia ; Kruse, Christoph ; Yasar, Yakub ; Löwe, Oliver ; Fork, Christian ; Van De Sluis, Bart ; Bremer, Rolf ; Weissmann, Norbert ; Shah, Ajay M. ; Jo, Hanjoong ; Brandes, Ralf P. ; Schröder, Katrin. / The NADPH oxidase Nox4 has anti-atherosclerotic functions. In: European Heart Journal. 2015 ; Vol. 36, No. 48. pp. 3447-3456.

Bibtex Download

@article{739ac58b097745108b7d895fb68e8c73,
title = "The NADPH oxidase Nox4 has anti-atherosclerotic functions",
abstract = "Aims Oxidative stress is thought to be a risk for cardiovascular disease and NADPH oxidases of the Nox family are important producers of reactive oxygen species. Within the Nox family, the NADPH oxidase Nox4 has a unique position as it is constitutively active and produces H2O2 rather than O2-. Nox4 is therefore incapable of scavenging NO and its low constitutive H2O2 production might even be beneficial. We hypothesized that Nox4 acts as an endogenous anti-atherosclerotic enzyme. Methods and results Tamoxifen-induced Nox4-knockout mice were crossed with ApoE-/- mice and spontaneous atherosclerosis under regular chow as well as accelerated atherosclerosis in response to partial carotid artery ligation under high-fat diet were determined. Deletion of Nox4 resulted in increased atherosclerosis formation in both models. Mechanistically, pro-atherosclerotic and pro-inflammatory changes in gene expression were observed prior to plaque development. Moreover, inhibition of Nox4 or deletion of the enzyme in the endothelium but not in macrophages resulted in increased adhesion of macrophages to the endothelial surface. Conclusions The H2O2-producing NADPH oxidase Nox4 is an endogenous anti-atherosclerotic enzyme. Nox4 inhibitors, currently under clinical evaluation, should be carefully monitored for cardiovascular side-effects.",
keywords = "ApoE, Arteriosclerosis, Inflammation, Lipids, NADPH oxidase, Reactive oxygen species, Remodelling",
author = "Christoph Sch{\"u}rmann and Flavia Rezende and Christoph Kruse and Yakub Yasar and Oliver L{\"o}we and Christian Fork and {Van De Sluis}, Bart and Rolf Bremer and Norbert Weissmann and Shah, {Ajay M.} and Hanjoong Jo and Brandes, {Ralf P.} and Katrin Schr{\"o}der",
year = "2015",
month = "12",
day = "21",
doi = "10.1093/eurheartj/ehv460",
language = "English",
volume = "36",
pages = "3447--3456",
journal = "European Heart Journal",
issn = "0195-668X",
publisher = "Oxford University Press",
number = "48",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - The NADPH oxidase Nox4 has anti-atherosclerotic functions

AU - Schürmann, Christoph

AU - Rezende, Flavia

AU - Kruse, Christoph

AU - Yasar, Yakub

AU - Löwe, Oliver

AU - Fork, Christian

AU - Van De Sluis, Bart

AU - Bremer, Rolf

AU - Weissmann, Norbert

AU - Shah, Ajay M.

AU - Jo, Hanjoong

AU - Brandes, Ralf P.

AU - Schröder, Katrin

PY - 2015/12/21

Y1 - 2015/12/21

N2 - Aims Oxidative stress is thought to be a risk for cardiovascular disease and NADPH oxidases of the Nox family are important producers of reactive oxygen species. Within the Nox family, the NADPH oxidase Nox4 has a unique position as it is constitutively active and produces H2O2 rather than O2-. Nox4 is therefore incapable of scavenging NO and its low constitutive H2O2 production might even be beneficial. We hypothesized that Nox4 acts as an endogenous anti-atherosclerotic enzyme. Methods and results Tamoxifen-induced Nox4-knockout mice were crossed with ApoE-/- mice and spontaneous atherosclerosis under regular chow as well as accelerated atherosclerosis in response to partial carotid artery ligation under high-fat diet were determined. Deletion of Nox4 resulted in increased atherosclerosis formation in both models. Mechanistically, pro-atherosclerotic and pro-inflammatory changes in gene expression were observed prior to plaque development. Moreover, inhibition of Nox4 or deletion of the enzyme in the endothelium but not in macrophages resulted in increased adhesion of macrophages to the endothelial surface. Conclusions The H2O2-producing NADPH oxidase Nox4 is an endogenous anti-atherosclerotic enzyme. Nox4 inhibitors, currently under clinical evaluation, should be carefully monitored for cardiovascular side-effects.

AB - Aims Oxidative stress is thought to be a risk for cardiovascular disease and NADPH oxidases of the Nox family are important producers of reactive oxygen species. Within the Nox family, the NADPH oxidase Nox4 has a unique position as it is constitutively active and produces H2O2 rather than O2-. Nox4 is therefore incapable of scavenging NO and its low constitutive H2O2 production might even be beneficial. We hypothesized that Nox4 acts as an endogenous anti-atherosclerotic enzyme. Methods and results Tamoxifen-induced Nox4-knockout mice were crossed with ApoE-/- mice and spontaneous atherosclerosis under regular chow as well as accelerated atherosclerosis in response to partial carotid artery ligation under high-fat diet were determined. Deletion of Nox4 resulted in increased atherosclerosis formation in both models. Mechanistically, pro-atherosclerotic and pro-inflammatory changes in gene expression were observed prior to plaque development. Moreover, inhibition of Nox4 or deletion of the enzyme in the endothelium but not in macrophages resulted in increased adhesion of macrophages to the endothelial surface. Conclusions The H2O2-producing NADPH oxidase Nox4 is an endogenous anti-atherosclerotic enzyme. Nox4 inhibitors, currently under clinical evaluation, should be carefully monitored for cardiovascular side-effects.

KW - ApoE

KW - Arteriosclerosis

KW - Inflammation

KW - Lipids

KW - NADPH oxidase

KW - Reactive oxygen species

KW - Remodelling

UR - http://www.scopus.com/inward/record.url?scp=84952042542&partnerID=8YFLogxK

U2 - 10.1093/eurheartj/ehv460

DO - 10.1093/eurheartj/ehv460

M3 - Article

AN - SCOPUS:84952042542

VL - 36

SP - 3447

EP - 3456

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - 48

ER -

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