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http://doi.org/10.25358/openscience-7343
Autoren: | Brandt, Moritz Garlapati, Venkata Oelze, Matthias Sotiriou, Efthymios Knorr, Maike Kröller-Schön, Swenja Kossmann, Sabine Schönfelder, Tanja Morawietz, Henning Schulz, Eberhard Schultheiss, Heinz-Peter Daiber, Andreas Münzel, Thomas Wenzel, Philip |
Titel: | NOX2 amplifies acetaldehyde-mediated cardiomyocyte mitochondrial dysfunction in alcoholic cardiomyopathy |
Online-Publikationsdatum: | 11-Jul-2022 |
Erscheinungsdatum: | 2016 |
Sprache des Dokuments: | Englisch |
Zusammenfassung/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. |
DDC-Sachgruppe: | 610 Medizin 610 Medical sciences |
Veröffentlichende Institution: | Johannes Gutenberg-Universität Mainz |
Organisationseinheit: | FB 04 Medizin |
Veröffentlichungsort: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-7343 |
Version: | Published version |
Publikationstyp: | Zeitschriftenaufsatz |
Nutzungsrechte: | CC BY |
Informationen zu den Nutzungsrechten: | https://creativecommons.org/licenses/by/4.0/ |
Zeitschrift: | Scientific reports 6 |
Seitenzahl oder Artikelnummer: | Art. 32554 |
Verlag: | Nature Publishing Group |
Verlagsort: | London |
Erscheinungsdatum: | 2016 |
ISSN: | 2045-2322 |
URL der Originalveröffentlichung: | http://dx.doi.org/10.1038/srep32554 |
DOI der Originalveröffentlichung: | 10.1038/srep32554 |
Enthalten in den Sammlungen: | DFG-OA-Publizieren (2012 - 2017) |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | ||
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nox2_amplifies_acetaldehydeme-20220710204447406.pdf | 7.46 MB | Adobe PDF | Öffnen/Anzeigen |