Ethanol Feeding Compromises Cardiovascular Function; A Potential Role For Mitochondrial Topoisomerases

Alcoholism remains a significant health problem and represents the third leading cause of preventable deaths in the United States. Alcoholic cardiomyopathy (ACM) presents as decreased myocardial contractility, arrhythmias, and secondary non‐ischemic dilated cardiomyopathy leading to heart failure. Mitochondrial dysfunction is thought to have a significant role in the development and complications of ACM. To examine the impact of chronic ethanol exposure on the myocardial mitochondria, rats were assigned to control or ethanol feeding for up to 4 months. Ethanol feeding lead to significant decrease (p<.05) in M‐mode Fraction Shortening and Ejection Fraction. Chronic ethanol feeding lead to a decrease in some components of Cytochrome Oxidase. Ethanol feeding significantly increased mtDNA damage, without a change in mitochondrial copy number. Using isolated myocardial mitochondria, both mitochondrial dependent DNA cleavage and DNA relaxation were altered by ethanol feeding compared to controls. Immunoprecipitation of myocardial mitochondrial extracts using a topoisomerase I antibody partially blocked mitochondrial dependent DNA cleavage. Chronic ethanol feeding compromised mitochondrial function as a result of a decline in mtDNA integrity that appears to the consequence of altered mitochondrial topoisomerase function