miRNAs in Cardiac Contraction

This chapter aims to introduce the role of miRNAs in regulating cardiac contraction. Cardiac contraction is triggered by excitation–contraction coupling: the cascade of biological events that begins with cardiac action potential and ends with myocyte contraction and relaxation. Cardiac muscle contraction is determined by the intrinsic contractile proteins: α- and β-myosin heavy chain (αMHC and βMHC). αMHC and βMHC are encoded by MYH6 and MYH7 genes, respectively, and their expression is species specific and varies in response to developmental and pathophysiological signaling alterations. Remarkably, studies revealed that myosin genes not only encode the major contractile proteins of muscle, but also act more broadly to control muscle gene expression and performance through a network of intronic miRNAs: the transcripts from these genes all contain pre-miRNAs. On the other hand, the cytoskeleton of cardiac myocytes consists of actin, the intermediate filament desmin, the sarcomeric protein titin, and α- and β-tubulin, which form the microtubules by polymerization. The loss of integrity of the cytoskeleton, with a resultant loss of linkage of the sarcomere to the sarcolemma and extracellular matrix, would be expected to lead to contractile dysfunction. miRNAs have been found to regulate both the contractile proteins (miR-208 and miR-21) and cytoskeleton proteins (miR-1 and miR- 133) to regulate cardiac contraction.