MicroRNA regulation and cardiac calcium signaling: Role in cardiac disease and therapeutic potential

MicroRNAs (miRNAs) are emerging as key control molecules in the regulation of gene expression, and their role in heart disease is becoming increasingly evident. Given the critical role of Ca handling and signaling proteins in the maintenance of cardiac function, the targeting of such proteins by miRNAs would be expected to have important consequences. miRNAs have indeed been shown to control the expression of genes encoding important Ca handling and signaling proteins, and are themselves regulated by Ca-dependent processes. Ca-related miRNAs have been found to be significant pathophysiological contributors in conditions like myocardial ischemic injury, cardiac hypertrophy, heart failure, ventricular arrhythmogenesis, and atrial fibrillation. This review is a comprehensive analysis of the present knowledge concerning miRNA regulation of Ca handling processes, the participation of Ca-regulating miRNAs in the evolution of heart disease, the mutual relationship between Ca signaling and miRNAs in the control of cardiac function, and the potential value of miRNA-control of Ca handling as a therapeutic target.