Etiology of alcoholic cardiomyopathy: Mitochondria, oxidative stress and apoptosis

Abstract

Putative mechanisms leading to the development of alcoholic cardiomyopathy (ACM) include the interrelated cellular processes of mitochondria metabolism, oxidative stress and apoptosis. As mitochondria fuel the constant energy demands of this continually contracting tissue, it is not surprising that alcohol-induced molecular changes in this organelle contribute to cardiac dysfunction and ACM. As the causal relationship of these processes with ACM has already been established, the primary objective of this review is to provide an update of the experimental findings to more completely understand the aforementioned mechanisms. Accordingly, recent data indicate that alcohol impairs mitochondria function assessed by membrane potential and respiratory chain activity. Indictors of oxidative stress including superoxide dismutase, glutathione metabolites and malondialdehyde are also adversely affected by alcohol oftentimes in a sex-dependent manner. Additionally, myocardial apoptosis is increased based on assessment of TUNEL staining and caspase activity. Recent work has also emerged linking alcohol-induced oxidative stress with apoptosis providing new insight on the codependence of these interrelated mechanisms in ACM. Attention is also given to methodological differences including the dose of alcohol, experimental model system and the use of males versus females to highlight inconsistencies and areas that would benefit from establishment of a consistent model.

Keywords: Caspase; Ethanol; Heart; Reactive oxygen species; Respiratory chain.