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The NADPH oxidase Nox4 has anti-atherosclerotic functions

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Christoph Schürmann, Flavia Rezende, Christoph Kruse, Yakub Yasar, Oliver Löwe, Christian Fork, Bart Van De Sluis, Rolf Bremer, Norbert Weissmann, Ajay M. Shah, Hanjoong Jo, Ralf P. Brandes, Katrin Schröder

Original languageEnglish
Pages (from-to)3447-3456
Number of pages10
JournalEuropean Heart Journal
Volume36
Issue number48
Early online date17 Sep 2015
DOIs
Publication statusPublished - 21 Dec 2015

King's Authors

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.

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