Epigenetics in atrial fibrillation: A reappraisal

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia and an important cause of morbidity and mortality globally. Atrial remodeling includes changes in ion channel expression and function, structural alterations, and neural remodeling, which create an arrhythmogenic milieu resulting in AF initiation and maintenance. Current therapeutic strategies for AF involving ablation and antiarrhythmic drugs are associated with relatively high recurrence and proarrhythmic side effects, respectively. Over the last 2 decades, in an effort to overcome these issues, research has sought to identify the genetic basis for AF thereby gaining insight into the regulatory mechanisms governing its pathophysiology. Despite identification of multiple gene loci associated with AF, thus far none has led to a therapy, indicating additional contributors to pathology. Recently, in the context of expanding knowledge of the epigenome (DNA methylation, histone modifications, and noncoding RNAs), its potential involvement in the onset and progression of AF pathophysiology has started to emerge. Probing the role of various epigenetic mechanisms that contribute to AF may improve our knowledge of this complex disease, identify potential therapeutic targets, and facilitate targeted therapies. Here, we provide a comprehensive review of growing epigenetic features involved in AF pathogenesis and summarize the emerging epigenomic targets for therapy that have been explored in preclinical models of AF.