Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 288

triphosphatase MHC is the dominant isoform expressed in embryonic cardiomy-

ocytes, whereas faster ATPase

β

MHC is upregulated in postnatal cardiomyocytes. 28
Thyroid hormone T 3 stimulates

α

MHC transcription after
birth. Cardiac-specific miR208, encoded by an intron of the

α MHC and inhibits β

Mhc gene, controls
the expression of MYH7 gene that is elevated by physical stress and hypothy-
roidism [ 530 ]. MicroRNA-208 targets thyroid hormone receptor-associated protein
THRAP1 29

α

a regulator of the thyroid hormone receptor that hampers β MHC

expression.
During cardiac hypertrophy, miR23a, miR23b, miR24, miR195, miR199a, and
miR214 are upregulated, whereas miR150 and miR181b are downregulated [ 531 ].
In failing heart, 30 miR21, miR29b, miR129, miR210, miR211, miR212, and
miR423 are overexpressed, whereas miR30, miR182, and miR526 are underex-
pressed. The miR1 level increases during cardiac infarctions specifically in ischemic
regions [ 527 ]. Overexpression of miR1 increases the occurrence of postinfarct
arrhythmias and promotes arrhythmias in healthy hearts. Overexpression of miR1
slows conduction and depolarizes the plasma membrane, as it represses transcript
of the KCNJ2 gene that encodes the K IR 2.1 subunit of K + channel, which sets
the resting membrane potential, and of GJA1, which encodes connexin-43 of gap
junctions.
Many microRNAs that are mainly produced by cardiac non-myocytes participate
in wall remodeling. In a mouse model of cardiac failure, miR21 is upregulated
and decreases the percentage of apoptotic fibroblasts, thereby favoring cardiac
fibrosis. MicroRNA-21 has an anti-apoptotic effect that results from activation
of extracellular signal-regulated kinase following repression of an inhibitor of
the Ras-ERK pathway, sprouty homolog Spry1 [ 533 ]. Expression of Spry1 is
precluded in failing human myocardium. Subsequently, enhanced activity of the
ERK pathway promotes fibroblast survival and growth factor secretion that can
cause interstitial fibrosis and cardiomyocyte hypertrophy due to growth factors
released from fibroblasts. In addition, miR21 is upregulated in cardiac fibroblasts
after myocardial ischemia-reperfusion injury [ 534 ]. MicroRNA-21 represses PTen
phosphatase that precludes PI3K-PKB signaling and MMP2 expression in cardiac
fibroblasts.

28 The

MHC is downregulated.
29 A.k.a. mediator complex subunit MED13, mediator of RNA polymerase-2 transcription subunit-
13, 250-kDa component of activator-recruited cofactor ARC250, 250-kDa vitamin-D3 receptor-
interacting protein complex component

β MHC level rises during cardiac diseases when α

DRIP250, and 240-kDa thyroid hormone receptor-

associated protein complex TRAP240.
30 Heart failure is a defect in proper blood filling and/or ejection. This progressive disorder is
initiated by myocardial injury, most commonly caused by coronary artery disease, hypertension,
and genetic factors.