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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 (O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2022\u2212)<\/jats:sup>\n                    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\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) were fed a 2% EtOH diet for 5 weeks creating an ACA-overload. 2% EtOH-fed ALDH-2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    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 91\n                    <jats:sup>phox<\/jats:sup>\n                    (NOX2\/gp91\n                    <jats:sup>phox<\/jats:sup>\n                    ) subunit expression compared to 2% EtOH-fed C57BL\/6 mice. Echocardiography revealed that ALDH-2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    \/gp91\n                    <jats:sup>phox\u2212\/\u2212<\/jats:sup>\n                    mice were protected from ACA-overload-induced HF after 5 weeks of 2% EtOH-diet, demonstrating that NOX2-derived O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2022\u2212<\/jats:sup>\n                    contributes to the development of ACM. Translated to human pathophysiology, we found increased gp91\n                    <jats:sup>phox<\/jats:sup>\n                    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\/gp91\n                    <jats:sup>phox<\/jats:sup>\n                    . NOX2\/gp91\n                    <jats:sup>phox<\/jats:sup>\n                    therefore might be a potential pharmacological target to treat ACM.\n                  <\/jats:p>","DOI":"10.1038\/srep32554","type":"journal-article","created":{"date-parts":[[2016,9,14]],"date-time":"2016-09-14T04:41:10Z","timestamp":1473828070000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["NOX2 amplifies acetaldehyde-mediated cardiomyocyte mitochondrial dysfunction in alcoholic cardiomyopathy"],"prefix":"10.1038","volume":"6","author":[{"given":"Moritz","family":"Brandt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkata","family":"Garlapati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Oelze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efthymios","family":"Sotiriou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Knorr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swenja","family":"Kr\u00f6ller-Sch\u00f6n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Kossmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Sch\u00f6nfelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Morawietz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eberhard","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz-Peter","family":"Schultheiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Daiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"M\u00fcnzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Wenzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,9,14]]},"reference":[{"key":"BFsrep32554_CR1","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1378\/chest.121.5.1638","volume":"121","author":"MR Piano","year":"2002","unstructured":"Piano, M. 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