Alcoholic Cardiomyopathy: Disrupted Protein Balance and Impaired Cardiomyocyte Contractility

Abstract

Alcoholic cardiomyopathy (ACM) can develop after consumption of relatively large amounts of alcohol over time or from acute binge drinking. Of the many factors implicated in the etiology of ACM, chronic perturbation in protein balance has been strongly implicated. This review focuses on recent contributions (since 2010) in the area of protein metabolism and cardiac function related to ACM. Data reviewed include that from in vitro and preclinical in vivo animal studies where alcohol or an oxidative metabolite was studied and outcome measures in either cardiomyocytes or whole heart pertaining to protein synthesis or degradation were reported. Additionally, studies on the contractile properties of cardiomyocytes were also included to link signal transduction with function. Methodological differences including the potential impact of sex, dosing and duration/timing of alcohol administration are addressed. Acute and chronic alcohol consumption decreases cardiac protein synthesis and/or activation of proteins within the regulatory mammalian/mechanistic target of rapamycin complex (mTORC1) pathway. Albeit limited, evidence suggests that myocardial protein degradation via the ubiquitin pathway is not altered, while autophagy may be enhanced in ACM. Alcohol impairs ex vivo cardiomyocyte contractility in relation to its metabolism and expression of proteins within the growth factor pathway. Dysregulation of protein metabolism, including the rate of protein synthesis and autophagy, may contribute to contractile deficits and is a hallmark feature of ACM meriting additional sex-inclusive, methodologically consistent studies.

Alcoholism: A Multi-Systemic Cellular Insult to Organs

“…Thus, improper calcium channel expression and activity may contribute to alcohol-induced cardiomyopathy. In this regard, it was suggested that the dysregulation of protein synthesis and autophagy contribute to the reduced contractility seen with high alcohol exposure [ 39 ].…”

Chronic heavy alcohol consumption and asymptomatic cardiovascular effects: An observational study

“…Major mechanisms implicated in the development of alcoholic cardiomyopathy include the direct toxic effect of ethanol and it metabolites (acetaldehyde and acetate) on the myocardium; vitamin (thiamine) and mineral (selenium) deficiencies as well as electrolyte (Mg, P, K) imbalance-deficits seen in heavy alcohol users; additional toxic effect of substances such as lead or cobalt found in alcoholic beverages; and genetic predisposition for ethanol toxicity (e.g. ACE gene) [17,20]. Chronic and intense toxic effects lead to systolic dysfunction and dilated cardiomyopathy [17,18,20].…”

Alcoholism: A Multi-Systemic Molecular Insult to Organ Damage

“…Thus, improper calcium channel expression and activity may contribute to alcohol-induced cardiomyopathy. In thid regard, it was suggested that dysregulation in protein synthesis and autophagy contribute to the reduced contractility seen with high alcohol exposure (Steiner JL et al, 2017).…”