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dc.contributor.authorHafstad, Anne Dragøy
dc.contributor.authorHansen, Synne Simonsen
dc.contributor.authorLund, Jim
dc.contributor.authorSantos, Celio X.C.
dc.contributor.authorBoardman, Neoma Tove
dc.contributor.authorShah, Ajay M.
dc.contributor.authorAasum, Ellen
dc.date.accessioned2021-02-24T14:36:47Z
dc.date.available2021-02-24T14:36:47Z
dc.date.issued2020-02-19
dc.description.abstractObesity and diabetes are independent risk factors for cardiovascular diseases, and they are associated with the development of a specific cardiomyopathy with elevated myocardial oxygen consumption (MVO<sub>2</sub>) and impaired cardiac efficiency. Although the pathophysiology of this cardiomyopathy is multifactorial and complex, reactive oxygen species (ROS) may play an important role. One of the major ROS-generating enzymes in the cardiomyocytes is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), and many potential systemic activators of NOX2 are elevated in obesity and diabetes. We hypothesized that NOX2 activity would influence cardiac energetics and/or the progression of ventricular dysfunction following obesity. Myocardial ROS content and mechanoenergetics were measured in the hearts from diet-induced-obese wild type (DIO<sub>WT</sub>) and global NOK2 knock-out mice (DIO<sub>KO</sub>) and in diet-induced obese C57BL/6J mice given normal water (DIO) or water supplemented with the NOX2-inhibitor apocynin (DIO<sub>APO</sub>). Mitochondrial function and ROS production were also assessed in DIO and DIOAPO mice. This study demonstrated that ablation and pharmacological inhibition of NOX2 both improved mechanical efficiency and reduced MVO<sub>2</sub> for non-mechanical cardiac work. Mitochondrial ROS production was also reduced following NOX2 inhibition, while cardiac mitochondrial function was not markedly altered by apocynin-treatment. Therefore, these results indicate a link between obesity-induced myocardial oxygen wasting, NOX2 activation, and mitochondrial ROS.en_US
dc.identifier.citationHafstad, Hansen, Lund, Santos, Boardman, Shah, Aasum. NADPH oxidase 2 mediates myocardial oxygen wasting in obesity. Antioxidants. 2020;9(2):1-17en_US
dc.identifier.cristinIDFRIDAID 1845375
dc.identifier.doi10.3390/antiox9020171
dc.identifier.issn2076-3921
dc.identifier.urihttps://hdl.handle.net/10037/20596
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.relation.journalAntioxidants
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Cardiology: 771en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Kardiologi: 771en_US
dc.titleNADPH oxidase 2 mediates myocardial oxygen wasting in obesityen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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