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. This article is part of a Special Issue entitled: Cardiomyocyte biology: new pathways of differentiation and regeneration edited by Marijke Brinkm, Marcus C. Schaub, and Christian Zuppinger.
|Journal||Biochimica et Biophysica Acta. Molecular Cell Research|
|Early online date||1 Jan 2019|
|Publication status||Published - Mar 2020|