Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 291

The Z disc is a nodal point for signaling, in addition to its structural role in the
maintenance of sarcomeres. The thin filament is also composed of tropomyosin
and troponin.
Alternative splicing is involved in cardiac adaptation. Isoform switch of sar-
comeric titin participate in adjustment to ventricular filling. RNA-binding motif-
containing protein RBM20 regulates titin splicing [ 541 ]. Abnormal mRNA splicing
that results from mutations in the Rbm20 gene produces pathological titin isoform
and heart failure.
The RNA-binding protein, RBM24, 37 contributes to the regulation of cardiac
gene expression and sarcomeric assembly, hence cardiac contractility [ 542 ]. It con-
trols the expression of several genes that encode constituents and regulators of the
Z disc. Tissue-specific protein RBM24 is upregulated during the differentiation of
human embryonic stem cells into cardiomyocytes. Agent RBM24 also intervenes
in skeletal muscle differentiation via the myogenic regulatory factor, myogenin.
Whereas the relatively small set of myogenic regulatory factors, such as MyoD and
myogenin, governs skeletal muscle differentiation, the myocarde development is
controlled by numerous transcription factors. In addition, RBM24 is also involved
in vasculo- and angiogenesis.

6.1.9 Cardiac Progenitor Cells and Precursors

Cardiomyocytes come from the primary and secondary heart fields in the embryo
[ 543 ]. Multipotent progenitor cells generate the 4 major cell types of the heart:
cardiomyocytes as well as nodal, smooth muscle, and endothelial cells.
Cardiac progenitors express the transcription factors NKx2-5 and insulin gene
enhancer LIM homeobox protein Islet-1 (Isl1). Factor NKx2.5 is activated in
multipotent cardiac progenitor cells of early embryos. NKx2.5 cells and their

progeny populate the precardiac mesoderm located dorsal to the cardiac region and
developing heart tube. Factor Isl1 is expressed transiently in multipotent cardiac
progenitor cells before their differentiation. Very-low-frequency electromagnetic
field raises metabolic activity in cardiac stem cells in vitro [ 544 ].
Distinct cardiac lineages, such as first and Isl1-expressing second lineage, exist
according to timing of entry into the heart and differentiation. Second heart field
progenitors generate cardiomyocytes that reside in the outflow tract, ventricles, and
atria. Proepicardium and epicardium are sources of coronary progenitors and cardiac
fibroblasts. 38
Both embryonic and postnatal cardiovascular progenitor cells characterized by
the expression of the transcription factor Islet-1 can differentiate into cardiac smooth

+

37 RMB24 has 2 known variants (Rbm24a and Rbm24b).
38 Epicardial cells migrate from the proepicardium, an outgrowth of the septum transversum, and
spread over the heart surface.