Epigenetic regulation of heart failure

Abstract

Purpose of review The studies on chromatin-modifying enzymes and how they respond to different stimuli within the cell have revolutionized our understanding of epigenetics. In this review, we provide an overview of the recent studies on epigenetic mechanisms implicated in heart failure. Recent findings We focus on the major mechanisms and the conceptual advances in epigenetics as evidenced by studies in humans and mouse models of heart failure. The significance of epigenetic modifications and the enzymes that catalyze them is also discussed. New findings from the studies of histone lysine demethylases demonstrate their significance in regulating fetal gene expression, as well as their aberrant expression in adult hearts during HF. Similarly, the relevance of histone deacetylases inhibition in heart failure and the role of HDAC6 in cardio-protection are discussed. Finally, the role of LMNA (lamin A/C), a nuclear membrane protein that interacts with chromatin to form hundreds of large chromatin domains known as lamin-associated domains (LADs), and 3D genome structure in epigenetic regulation of gene expression and heart failure is discussed. Summary Epigenetic modifications provide a mechanism for responding to stress and environmental variation, enabling reactions to both external and internal stimuli, and their dysregulation can be pathological as in heart failure. To gain a thorough understanding of the pathological mechanisms and to aid in the development of targeted treatments for heart failure, future research on studying the combined effects of numerous epigenetic changes and the structure of chromatin is warranted.