Role of HDACs in cardiac electropathology: Therapeutic implications for atrial fibrillation.

Perpetuation of atrial fibrillation (AF) is caused by electropathology, which is defined as impairment of electrical activation caused by structural and metabolic remodeling of cardiomyocytes. We previously dissected the molecular mechanisms underlying electropathology and identified an important role for histone deacetylases (HDACs). HDACs catalyze the removal of acetyl-groups from lysine residues within nucleosomal histone tails and many non-histone proteins. Various HDAC inhibitors are efficacious in attenuating electropathology, and improve contractile function in experimental AF. Emerging evidence reveals novel mechanisms by which HDAC inhibitors prevent cardiac electropathology and thereby benefit the heart during AF. These mechanisms include post-translational modification of contractile and structural proteins and changes in gene expression. In this review paper, we summarize recent findings on novel functions of zinc-dependent HDACs in electropathology and discuss the potential for pharmacological HDAC inhibition as a strategy to treat AF. • Perpetuation of atrial fibrillation (AF) is caused by electropathology. • HDAC inhibitors attenuate electropathology in AF and other cardiac diseases. • HDACs deacetylate contractile and structural proteins in the heart. • HDACs regulate gene expression by targeting transcription factors in the heart. • HDAC3 and HDAC6 represent novel therapeutic targets for AF. [ABSTRACT FROM AUTHOR]