Transgenic Overexpression of Aldehyde Dehydrogenase-2 Rescues Chronic Alcohol Intake–Induced Myocardial Hypertrophy and Contractile Dysfunction
- 14 April 2009
- journal article
- retracted article
- Published by Wolters Kluwer Health in Circulation
- Vol. 119 (14) , 1941-1949
- https://doi.org/10.1161/circulationaha.108.823799
Abstract
Background— Chronic alcoholism leads to the onset and progression of alcoholic cardiomyopathy through toxic mechanisms of ethanol and its metabolite, acetaldehyde. This study examined the impact of altered acetaldehyde metabolism through systemic transgenic overexpression of aldehyde dehydrogenase-2 (ALDH2) on chronic alcohol ingestion–induced myocardial damage. Methods and Results— ALDH2 transgenic mice were produced with the chicken β-actin promoter. Wild-type FVB and ALDH2 mice were placed on a 4% alcohol diet or a control diet for 14 weeks. Myocardial and cardiomyocyte contraction, intracellular Ca2+ handling, histology (hematoxylin and eosin, Masson trichrome), protein damage, and apoptosis were determined. Western blot was used to monitor the expression of NADPH oxidase, calcineurin, apoptosis-stimulated kinase (ASK-1), glycogen synthase kinase-3β (GSK-3β), GATA4, and cAMP-response element binding (CREB) protein. ALDH2 reduced the chronic alcohol ingestion–induced elevation in plasma and tissue acet...Keywords
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