MicroRNA regulation of cardiac conduction and arrhythmias

MicroRNAs are now recognized as important regulators of cardiovascular genes with critical roles in normal development and physiology, as well as disease development. MicroRNAs (miRNAs) are small noncoding RNAs approximately 22 nucleotides in length that regulate expression of target genes through sequence-specific hybridization to the 3' untranslated region of messenger RNAs and either block translation or direct degradation of their target messenger RNA. They have been shown to participate in cardiovascular disease pathogenesis including atherosclerosis, coronary artery disease, myocardial infarction, heart failure, and cardiac arrhythmias. Broadly defined, cardiac arrhythmias are a variation from the normal heart rate or rhythm. Arrhythmias are common and result in significant morbidity and mortality. Ventricular arrhythmias constitute a major cause for cardiac death, particularly sudden cardiac death in the setting of myocardial infarction and heart failure. As advances in pharmacologic, device, and ablative therapy continue to evolve, the molecular insights into the basis of arrhythmia is growing with the ambition of providing additional therapeutic options. Electrical remodeling and structural remodeling are identified mechanisms underlying arrhythmia generation; however, published studies focusing on miRNAs and cardiac conduction are sparse. Recent studies have highlighted the role of miRNAs in cardiac rhythm through regulation of key ion channels, transporters, and cellular proteins in arrhythmogenic conditions. This article aims to review the studies linking miRNAs to cardiac excitability and other processes pertinent to arrhythmia.