Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 287

Tabl e 6. 4. MicroRNAs and heart structure and activity in mice (Sources: [ 526 - 530 ]). MicroR-
NAs regulate cardiogenesis and growth, conduction of the electrochemical signal, and myocardium
contraction. They include muscle-specific microRNAs (miR1, miR133, and miR208) and other
microRNAs (e.g., miR18b, miR21, and miR195). Cardiac miR1 targets a gap junction protein
and cardiac transcription factor Irx5 that regulates the nodal tissue. Overexpression of miR1 is
associated with cardiac arrhythmia. Loss in miR1-2 leads to ventricular septum defects (septal
holes), cardiomyocyte hyperplasia, and abnormal conduction in the ventricular nodal tissue.
MicroRNA-133 prevents cardiac hypertrophy in response to mechanical and chemical stimuli.
Heart-specific miR208 is transcribed from a sequence of the intron of the gene of the heavy chain
of -myosin heavy chain during stress

or hypothyroidism. Hyperpolarization-activated and cyclic nucleotide-gated channels (HCN) are
responsible for depolarizing pacemaker “funny” current i f .
Type

α -myosin. MicroRNA-208 is required for the expression of β

Cardiac effect

MicroRNA-1 Growth, conduction

(GJA1 [Cx43] and KCNJ2 [K IR 2.1]),
automaticity (HCN2 and HCN4 [ i f ])

MicroRNA-1-2 Morphogenesis, CMC number, conduction

MicroRNA-133 Growth, repolarization

(KCNQ1 [K V 7.1] and KCNE1 [minK; i K , s ])
(KCNH2 [K V 11.1; i K , r ]),
automaticity (HCN2 [ i f ])

MicroRNA-208 Growth

MicroRNA-138 is required to establish distinct identity of cardiac structures
and appropriate chamber-specific gene expression patterns during cardiogene-
sis [ 532 ]. MicroRNA-138 represses transcripts specific to atrioventricular canal in
the developing ventricle.
Action of miR1 is dose sensitive [ 528 ]. MicroRNA-1-2 regulates not only
cardiogenesis, but also the cardiomyocyte cycle. In mouse embryos, homozygous
deletion of muscle-specific miR1-2 induces ventricular septal defects, possibly
due to an increased level of bHLHa26 transcription factor or HAND2 regulator).
Surviving mice exhibit cardiac arrhythmias caused by defects in potassium channels
resulting from increased abundance of the transcription factor Irx5, a repressor of
the KCND2 gene that encodes K V 4.2 channel. Moreover, they have an increased
rate of cardiomyocyte mitosis.
Muscle-specific miR1 and miR133 hinder myocardium growth. MicroRNA-
133 targets transcripts of RhoA and CDC42 GTPases that regulate cytoskeletal
dynamics during hypertrophy, as well as nuclear factor Negative elongation factor-A
(NElFa) 27 that is involved in cardiogenesis [ 529 ].
Cardiac contractility depends on the expression of 2 genes that encode myosin
heavy chain. Isoforms

MHC are contractile proteins of cardiomyocytes that
are regulated in an antithetical manner by various signals. The slower adenosine

α and β

27 A.k.a. Wolf-Hirschhorn syndrome candidate WHSC2.