Early-Stage Alcoholic Cardiomyopathy Highlighted by Metabolic Remodeling, Oxidative Stress, and Cardiac Myosin Dysfunction in Male Rats

TL;DR

This study shows that early alcohol exposure in rats causes heart muscle changes through metabolic shifts, oxidative stress, and myosin dysfunction.

Contribution

The study identifies early-stage metabolic and oxidative changes in alcoholic cardiomyopathy that precede visible heart damage.

Findings

Ethanol exposure increases mitochondrial lipid metabolism and causes mitochondrial structural impairments.

Cardiac myosin from ethanol-exposed rats shows reduced ATPase activity and increased protein oxidation.

Oxidation of healthy myosin leads to significant declines in its functional activity.

Abstract

Chronic ethanol use can lead to alcoholic cardiomyopathy (ACM), while the impact on the molecular and cellular aspects of the myocardium is unclear. Accordingly, male Sprague-Dawley rats were exposed to an ethanol-containing diet for 16 weeks and compared with a control group that was fed an isocaloric diet. Histological measurements from H&E slides revealed no significant differences in cell size. A proteomic approach revealed that alcohol exposure leads to enhanced mitochondrial lipid metabolism, and electron microscopy revealed impairments in mitochondrial morphology/density. Cardiac myosin purified from the hearts of ethanol-exposed animals demonstrated a 15% reduction in high-salt ATPase activity, with no significant changes in the in vitro motility and low-salt ATPase or formation of the super-relaxed (SRX) state. A protein carbonyl assay indicated a 20% increase in carbonyl incorporation, suggesting that alcohol may impact cardiac myosin through oxidative stress mechanisms. In vitro oxidation of healthy cardiac myosin revealed a dramatic decline in ATPase activity and in vitro motility, demonstrating a link between myosin protein oxidation and myosin mechanochemistry. Collectively, this study suggests alcohol-induced metabolic remodeling may be the initial insult that eventually leads to defects in the contractile machinery in the myocardium of ACM hearts.

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