Gutenberg Open Science: NOX2 amplifies acetaldehyde-mediated cardiomyocyte mitochondrial dysfunction in alcoholic cardiomyopathy

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7343

Full metadata record

DC Field	Value	Language
dc.contributor.author	Brandt, Moritz	-
dc.contributor.author	Garlapati, Venkata	-
dc.contributor.author	Oelze, Matthias	-
dc.contributor.author	Sotiriou, Efthymios	-
dc.contributor.author	Knorr, Maike	-
dc.contributor.author	Kröller-Schön, Swenja	-
dc.contributor.author	Kossmann, Sabine	-
dc.contributor.author	Schönfelder, Tanja	-
dc.contributor.author	Morawietz, Henning	-
dc.contributor.author	Schulz, Eberhard	-
dc.contributor.author	Schultheiss, Heinz-Peter	-
dc.contributor.author	Daiber, Andreas	-
dc.contributor.author	Münzel, Thomas	-
dc.contributor.author	Wenzel, Philip	-
dc.date.accessioned	2022-07-11T09:53:03Z	-
dc.date.available	2022-07-11T09:53:03Z	-
dc.date.issued	2016
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/7357	-
dc.description.abstract	Alcoholic cardiomyopathy (ACM) resulting from excess alcohol consumption is an important cause of heart failure (HF). Although it is assumed that the cardiotoxicity of the ethanol (EtOH)-metabolite acetaldehyde (ACA) is central for its development and progression, the exact mechanisms remain obscure. Murine cardiomyocytes (CMs) exposed to ACA or EtOH showed increased superoxide (O2•−) levels and decreased mitochondrial polarization, both being normalized by NADPH oxidase (NOX) inhibition. C57BL/6 mice and mice deficient for the ACA-degrading enzyme mitochondrial aldehyde dehydrogenase (ALDH-2−/−) were fed a 2% EtOH diet for 5 weeks creating an ACA-overload. 2% EtOH-fed ALDH-2−/− mice exhibited a decreased cardiac function, increased heart-to-body and lung-to-body weight ratios, increased cardiac levels of the lipid peroxidation product malondialdehyde (MDA) as well as increased NOX activity and NOX2/glycoprotein 91phox (NOX2/gp91phox) subunit expression compared to 2% EtOH-fed C57BL/6 mice. Echocardiography revealed that ALDH-2−/−/gp91phox−/− mice were protected from ACA-overload-induced HF after 5 weeks of 2% EtOH-diet, demonstrating that NOX2-derived O2•− contributes to the development of ACM. Translated to human pathophysiology, we found increased gp91phox expression in endomyocardial biopsies of ACM patients. In conclusion, ACM is promoted by ACA-driven mitochondrial dysfunction and can be improved by ablation of NOX2/gp91phox. NOX2/gp91phox therefore might be a potential pharmacological target to treat ACM.	en_GB
dc.description.sponsorship	DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	NOX2 amplifies acetaldehyde-mediated cardiomyocyte mitochondrial dysfunction in alcoholic cardiomyopathy	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-7343	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Scientific reports	de
jgu.journal.volume	6	de
jgu.pages.alternative	Art. 32554	de
jgu.publisher.year	2016	-
jgu.publisher.name	Nature Publishing Group	de
jgu.publisher.place	London	de
jgu.publisher.uri	http://dx.doi.org/10.1038/srep32554	de
jgu.publisher.issn	2045-2322	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
opus.date.modified	2019-05-16T07:49:35Z
opus.subject.dfgcode	00-000
opus.organisation.string	FB 04: Medizin: II. Medizinische Klinik und Poliklinik	de_DE
opus.organisation.string	FB 04: Medizin: Centrum für Thrombose und Hämostase (CTH)	de_DE
opus.organisation.string	FB 04: Medizin: Zentrum für Kardiologie	de_DE
opus.identifier.opusid	56433
opus.institute.number	0426
opus.institute.number	0463
opus.institute.number	0466
opus.metadataonly	false
opus.type.contenttype	Keine	de_DE
opus.type.contenttype	None	en_EN
opus.affiliated	Schulz, Eberhard
opus.affiliated	Daiber, Andreas
opus.affiliated	Münzel, Thomas
opus.affiliated	Wenzel, Philip
jgu.publisher.doi	10.1038/srep32554	de
jgu.organisation.ror	https://ror.org/023b0x485
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)

Files in This Item:

	File	Description	Size	Format
	nox2_amplifies_acetaldehydeme-20220710204447406.pdf		7.46 MB	Adobe PDF	View/Open

Show simple item record