Abstract 13236: Post-ischemic Cardiac Functional Changes Caused by Prior Chronic Alcohol Consumption Correlate with Alterations to Epigenetic Histone Modifications in the Heart
Chronic ethanol consumption in humans correlates with the occurrence of adverse cardiovascular events/mortality according to a J-shaped response curve. Moderate consumption generally provides cardio-protection while abstinence and high ethanol intake generate modest and higher cardiac risk, respectively. Clinical studies show that this effect persists following an acute myocardial infarction (AMI). However, the major theories (i.e. altered plasma lipid balance and coagulation) supporting the cardio-protection conferred by moderate ethanol both ignore the direct effects that ethanol may have on myocardial cell types. Recent findings have also suggested that chronic ethanol consumption interferes with cellular epigenetic programs although this has not yet been tested in the heart. Therefore, we tested whether chronic ethanol consumption could influence post-ischemic cardiac function in the mouse and whether chronic ethanol modulates the epigenetic status of cardiac cell types to induce phenotypic functional changes. Adult mice (C57Bl/6) were chronically fed a liquid diet containing 0%, 1% (moderate) or 5% (high) ethanol v/v% for 4 weeks and then endured a 60 minute ischemia/reperfusion injury. Serial echocardiographic assessments at 1, 2 and 4 weeks post-AMI revealed improvements in the moderate (1%) ethanol group as compared to the 0% group. Conversely, the 5% ethanol group showed vastly worse cardiac function. To explore the cellular basis of these observed functional changes, primary cardiac fibroblasts (PCFBs) treated chronically (5 days) with ethanol in vitro (i.e. 0%, 0.1% (moderate) or 0.5% (high) ethanol v/v) displayed robust changes in their epigenetic histone-modification profiles indicating a high likelihood of potential changes in cellular gene expression. Supporting this assertion were studies showing that conditioned media from ethanol treated PCFBs alter the tube forming ability of HUVECs based on the original ethanol dose with moderate ethanol enhancing, and high ethanol reducing tube formation compared to the 0% condition. These data suggest that chronic ethanol directly invokes epigenetic changes in PCFBs that likely modifies the contribution these cells make to cardiac repair processes following AMI.
- © 2013 by American Heart Association, Inc.