Sex‐dependent molecular alterations during development of alcoholic cardiomyopathy in rat

Abstract

Excessive, chronic alcohol consumption can result in alcoholic heart muscle disease (AHMD) and, ultimately, heart failure. Functional and structural damage to the myocardium is consistent with a shift in myocardial protein expression and activity that occurs as the disease progresses. The current study aims to link alcohol‐induced alterations in expression of specific proteins with the differences between male and female using a chronic rat model. This study uses isobaric tags for relative and absolute quantitation (iTRAQ) followed by mass spectrometry to delineate shifts in protein expression in rat myocardium as a consequence of chronic (18 week) alcohol intake. Echocardiography allowed the early detection of changes to the heart. Consuming alcohol for 16 weeks lowered stroke volume and left ventricular diastolic volume in both sexes. Males showed additional significant declines in left ventricular mass and end‐diastolic dimension. At the end of the alcohol‐feeding regimen, hearts were fractionated into myofibrillar, sarcoplasmic, mitochondrial, and nuclear fractions. Early interpretation of the proteomic data obtained from mitochondrial fractions identified variations in structural proteins as well as proteins involved in oxidative phosphorylation and electron transport.NIAAA R01 AA012814 (TCV) and PA Dept of Health Tobacco Settlement Award (RLF)