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.
