title: Enzymes and signal pathways in the pathogenesis of alcoholic cardiomyopathy.
abstract: Owing to its acute psychotropic effects, ethanol is the most frequently consumed toxic agent worldwide. However, excessive alcohol intake results in an array of health, social, and economic consequences, which are related to its property as an addictive substance. It has been well established that exposure to high levels of alcohol for a long period leads to the onset and progression of nonischemic cardiomyopathy through direct toxic mechanisms of ethanol and its metabolite, acetaldehyde. Excessive alcohol ingestion causes myocardial damage including disruptions of the myofibrillar architecture and is associated with reduced myocardial contractility and decreased ejection volumes. Key features of alcoholic cardiomyopathy are cardiac hypertrophy and ventricular dilatation, and the disease is manifested mainly as cardiomegaly, congestive heart failure, and even cardiac death. Mechanisms that have been postulated to underlie the pathogenesis of alcoholic cardiomyopathy include apoptosis, mitochondrial alterations, acetaldehyde protein adduct formation, oxidative stress, and imbalances in fatty acid metabolism. In the following, we give a brief overview of the molecular effects of ethanol-metabolizing enzymes and their impact on myocardial signal transduction pathways.
authors.affiliation: Psychosomatic Medicine and Psychotherapy, German Centre for Cardiovascular Research, University of Göttingen Medical Centre, von-Siebold-Str. 5, 37075, Göttingen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Leibing
authors.affiliation: Psychosomatic Medicine and Psychotherapy, German Centre for Cardiovascular Research, University of Göttingen Medical Centre, von-Siebold-Str. 5, 37075, Göttingen, Germany. thomas.meyer@med.uni-goettingen.de.
authors.forename: T
authors.initials: T
authors.lastname: Meyer
mesh_terms: D000818:Animals; D002310:Cardiomyopathy, Alcoholic / Q000201:enzymology* / Q000209:etiology; D000431:Ethanol / Q000506:poisoning*; D006321:Heart / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008955:Models, Cardiovascular; D009097:Multienzyme Complexes / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D009097:Multienzyme Complexes; D000431:Ethanol
keywords: Alcohol dehydrogenase; Alcoholic cardiomyopathy; Aldehyde dehydrogenase; STAT3 transcription factor; Signal transduction