Long non-coding RNAs as new regulators of cardiac electrophysiology and arrhythmias: Molecular mechanisms, therapeutic implications and challenges.

Long non-coding RNAs (lncRNAs or lncRs) as a new class of regulatory transcripts have been intensively studied for their roles in cardiovascular biology in the past decade. We now know that lncRNAs are significantly implicated in diverse cardiovascular conditions and associated risk factors, including myocardial infarction, coronary heart disease, atherosclerosis/coronary artery disease, vascular disease, cardiac hypertrophy, heart failure, etc. Though in its early stage, research on control of cardiac electrophysiology by lncRNAs has generated some interesting observations and mechanistic insight of significant relevance to translational medicine. This review article focuses on lncRNA regulation of cardiac electrophysiology and arrhythmias with brief discussion on some fundamental aspects of relevant background information for better understanding of the subject. It provides critical analysis of published studies in the literature together with unpublished observations from our own laboratories. In addition to discuss the phenotypes associated with deregulation of lncRNAs, we also try to dissect out the cellular and molecular mechanisms for lncRNAs as regulators of arrhythmogenesis. This review then further touches on the therapeutic implications of lncRNAs and potential strategies for the development of lncRNA-based drugs. Finally, future directions to lncRNA research on cardiac electrophysiology and arrhythmias are anticipated.