The NADPH oxidase Nox4 has anti-atherosclerotic functions

Autor: Bart van de Sluis, Ajay M. Shah, Katrin Schröder, Norbert Weissmann, Flávia Rezende, Christoph Kruse, Rolf Bremer, Ralf P. Brandes, Christian Fork, Yakub Yasar, Oliver Löwe, Hanjoong Jo, Christoph Schürmann
Přispěvatelé: Center for Liver, Digestive and Metabolic Diseases (CLDM), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)
Rok vydání: 2015
Předmět:
Arteriosclerosis
medicine.disease_cause
DISEASE
ANGIOGENESIS
ACTIVATION
Mice
chemistry.chemical_compound
Leukocytes
Medicine
PROTECTION
Mice
Knockout
chemistry.chemical_classification
Oxidase test
NADPH oxidase
biology
NOX4
Lipids
DEFICIENCY
Carotid Arteries
medicine.anatomical_structure
NADPH Oxidase 4
cardiovascular system
medicine.symptom
Cardiology and Cardiovascular Medicine
ApoE
medicine.medical_specialty
Endothelium
Inflammation
Nitric oxide
Apolipoproteins E
Internal medicine
Cell Adhesion
Animals
SUPEROXIDE-PRODUCTION
Ligation
Reactive oxygen species
NITRIC-OXIDE
urogenital system
business.industry
Remodelling
NADPH Oxidases
Hydrogen Peroxide
Atherosclerosis
Microarray Analysis
Oxidative Stress
Endocrinology
chemistry
Immunology
biology.protein
Reactive Oxygen Species
business
Oxidative stress
APOE(-/-) MICE
Zdroj: European Heart Journal, 36(48), 3447-3456. Oxford University Press
ISSN: 1522-9645
0195-668X
Popis: 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 O-2(-). 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.
Databáze: OpenAIRE
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