The Importance of Autophagy and Proteostasis in Metabolic Cardiomyopathy

Abstract

Metabolic cardiomyopathy and other heart disorders are associated with proteostasis derailment and subsequent autophagy. Proteostasis is a process of protein homeostasis, and autophagy is a mechanism of self-degradation for surviving cells facing stressful conditions. Metabolic challenges have been linked to excess reactive oxygen species. Cardiomyocyte proteotoxicity, an important underlying pathologic mechanism in cardiac disease, is characterized by chronic accumulation of misfolded or unfolded proteins that can lead to proteotoxic formation or aggregation of soluble peptides. Autophagic processes are mediated by the ubiquitin-proteasome and autophagy-lysosome systems, fundamental for cardiac adaptation to physiological and pathological stress. Cellular proteostasis alterations in cardiomyopathy are represented by myocardial remodeling and interstitial fibrosis with reduced diastolic function and arrhythmias. Autophagy regulation may be a potential therapeutic strategy for metabolic cardiomyopathy necessary for the treatment of fibrosis and cardiac tissue remodeling alterations. Furthermore, autophagy has been shown to be active in the perimeter of cardiovascular fibrotic tissue as mechanism of fibrosis recovery and scarring secondary to cell apoptosis. In the present work, we review the current knowledge on the role of autophagy and proteostasis in the pathogenesis of heart failure to resolve the ever-expanding epidemic of metabolic cardiomyopathy and heart failure associated with substantial morbidity and mortality.