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Enzymes and signal pathways in the pathogenesis of alcoholic cardiomyopathy

Enzyme und Signalwege in der Pathogenese der alkoholischen Kardiomyopathie

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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.

Zusammenfassung

Aufgrund seiner akuten psychotropen Effekte ist Ethylalkohol eine der meistkonsumierten toxischen Substanzen weltweit, doch seine exzessive Aufnahme führt zu vielfältigen negativen gesundheitlichen, sozialen und ökonomischen Folgen. Es ist gut belegt, dass der längerfristige Konsum größerer Mengen von Alkohol mit der Entstehung und Progression einer nichtischämischen Kardiomyopathie einhergeht, die über direkte toxische Effekte des Ethanols und seines Metaboliten Azetylaldehyd vermittelt wird. Übermäßiger Alkoholkonsum verursacht myokardiale Schäden einschließlich Störungen der myofibrillären Architektur und ist mit einer verminderten myokardialen Kontraktilität und reduzierten Ejektionsvolumina assoziiert. Hauptmerkmale der alkoholinduzierten Kardiomyopathie sind kardiale Hypertrophie und ventrikuläre Dilatation; dementsprechend manifestiert sich die Erkrankung als Kardiomegalie und kongestive Herzinsuffizienz bis hin zum kardialen Tod. Als Mechanismen, die der Pathogenese der Alkoholkardiomyopathie zugrunde liegen, wurden Apoptose, mitochondriale Veränderungen, azetaldehydinduzierte Adduktbildung von Proteinen, oxidativer Stress sowie Ungleichgewichte im Fettstoffwechsel angenommen. Im Folgenden wird ein kurzer Überblick über die molekularen Effekte der beteiligten ethanolmetabolisierenden Enzyme und die von diesen ausgehenden Einflüsse auf myokardiale Signaltransduktionswege gegeben.

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  1. Psychosomatic Medicine and Psychotherapy, German Centre for Cardiovascular Research, University of Göttingen Medical Centre, von-Siebold-Str. 5, 37075, Göttingen, Germany

    E. Leibing &  T. Meyer

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  1. E. Leibing
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  2. T. Meyer
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Correspondence to T. Meyer.

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E. Leibing and T. Meyer state that there are no conflicts of interest.

The accompanying manuscript does not include studies on humans or animals.

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Leibing, E., Meyer, T. Enzymes and signal pathways in the pathogenesis of alcoholic cardiomyopathy. Herz 41, 478–483 (2016). https://doi.org/10.1007/s00059-016-4459-8

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