Autophagy in Heart Failure: Insights into Mechanisms and Therapeutic Implications

Abstract

Autophagy, a dynamic and complex process responsible for the clearance of damaged cellular components, plays a crucial role in maintaining myocardial homeostasis. In the context of heart failure, autophagy has been recognized as a response mechanism aimed at counteracting pathogenic processes and promoting cellular health. Its relevance has been underscored not only in various animal models, but also in the human heart. Extensive research efforts have been dedicated to understanding the significance of autophagy and unravelling its complex molecular mechanisms. This review aims to consolidate the current knowledge of the involvement of autophagy during the progression of heart failure. Specifically, we provide a comprehensive overview of published data on the impact of autophagy deregulation achieved by genetic modifications or by pharmacological interventions in ischemic and non-ischemic models of heart failure. Furthermore, we delve into the intricate molecular mechanisms through which autophagy regulates crucial cellular processes within the three predominant cell populations of the heart: cardiomyocytes, cardiac fibroblasts, and endothelial cells. Finally, we emphasize the need for future research to unravel the therapeutic potential associated with targeting autophagy in the management of heart failure.