Role of autophagy and regulatory mechanisms in alcoholic cardiomyopathy

Alcoholism is accompanied with a high incidence of cardiac morbidity and mortality due to the development of alcoholic cardiomyopathy, manifested as dilation of one or both ventricles, reduced ventricular wall thickness, myofibrillary disarray, interstitial fibrosis, hypertrophy and contractile dysfunction. Several theories have been postulated for the etiology of alcoholic cardiomyopathy including ethanol/acetaldehyde toxicity, mitochondrial production of reactive oxygen species, oxidative injury, apoptosis, impaired myofilament Ca2+ sensitivity and protein synthesis, altered fatty acid extraction and deposition, as well as accelerated protein catabolism. In particular, buildup of long-lived or dysfunctional organelles has been reported to contribute to cardiac structural and functional damage following alcoholism. Removal of cell debris and defective organelles by autophagy is essential to the maintenance of cardiac homeostasis in physiological and pathological conditions. However, insufficient understanding is currently available with regards to the involvement of autophagy in the pathogenesis of alcoholic cardiomyopathy. This review summarizes the recent findings on the pathophysiological role of dysregulated autophagy in one set and development of alcoholic cardiomyopathy. A thorough understanding of how autophagy is affected in alcoholism, and subsequently, contributes to the pathogenesis of alcoholic heart injury, will offer therapeutic guidance towards the management of alcoholic cardiomyopathy.