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.

The Effects of Ethanol on the Heart: Alcoholic Cardiomyopathy

“…The resulting effect in those multiple sites may be additive and synergistic, increasing the final damage [20,52] (Figure 1). mitochondrial respiratory chain [100,109,110]. As a reflection of this metabolic derangement, cytoplasmic lipid droplets and glycogen deposits appear.…”

Mechanisms of toxic cardiomyopathy

“…Basic research is still ongoing to identify the mechanisms of alcohol-induced damage to the cardiomyocyte. It is now well accepted that the mechanisms are multifactorial and would include at least the following: apoptosis, alterations of the excitation-contraction coupling in cardiac myocytes, structural and functional alterations of the mitochondria and sarcoplasmic reticulum, changes in cytosolic calcium flows, changes in calcium sensitivity of myofilaments, alterations of mitochondrial oxidation, deregulation of protein synthesis, decrease of contractile proteins and disproportion between the different types of myofibrils, changes in the regulation of myosin ATPase, up-regulation of the L-type calcium channels, increase of oxidative stress, induction of ANP and p21 mRNA expression in ventricular myocardium, and activation of the renin-angiotensin system and of the sympathetic nervous system [38][39][40][41][42][43] The central role of individual susceptibility has been outlined. In order to explain this susceptibility, metabolic and genetic factors were investigated [44].…”

A modern view on the pathogenesis, diagnosis and treatment of alcoholic cardiomyopathy

“…В последние годы при изучении животных моделей обнаружены дополнительные признаки повреждения митохондрий в виде изменения их мембранного потенциала и активности ферментов дыхательной цепи, а также снижения биосинтеза АТФ [37]. Наблюдалось уменьшение содержания супероксиддисмутазы, метаболитов глутатиона и малонового диальдегида, а также перекисное окисление липидов, повышение образования свободных радикалов, активных форм кислорода.…”