Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 278

embryogenesis, is required for the formation of the cardiac jelly. This glycosamino-
glycan of the extracellular space regulates ligand availability. It interacts with
numerous matrix constituents such as versican, a major proteoglycan of the cardiac
jelly.
Small Ras GTPase is activated by receptor protein Tyr kinases to heighten
mesenchymal proliferation. It can then signal via MAPK modules. Neurofibromin-1
is a Ras-specific GTPase-activating protein (RasGAP) that inactivates Ras GTPase.
Neurofibromin-1 can diminish endothelial and/or mesenchymal cell proliferation.
Small Ras GTPase can also interact with NFAT2 to control gene transcription [ 485 ].
Neurofibromin-1 modulates the timing of NFAT2 intranuclear localization to avoid
hyperplasia of cardiac cushions.
Transcription factor Sox9, in conjunction with Sox5 and Sox6, targets the CHM1
gene in avascular tissue that encodes chondromodulin-1. 11 In the interstitial space,
chondromodulin-1 inhibits endothelial cell proliferation and angiogenesis [ 499 ].
Chondromodulin-1 expression persists in normal cardiac valves throughout life.
It is downregulated in degenerative cardiac valves. Loss in chondromodulin-1,
indeed, leads to vascularization, calcification, lipid deposition, and inflammation
of cardiac valves.
With its structural and functional heterogeneity, the heart achieves a coordinated
contraction of its myofiber population in the 2 in-series pumps with its twinned
chambers to eject blood in both circulations during each cycle. This composite
material is optimally organized. The activation phase of the myofibers matches their
mechanical heterogeneity for a suitable electromechanical coupling.

6.1.7 Postnatal Growth

During the fetal life, cardiomyocytes proliferate. Although from birth to adulthood
heart mass rises, cardiomyocyte proliferation slows around birth [ 500 ]. Most of
the postnatal increase in cardiomyocyte mass results from hypertrophy rather than
cell division, whereas other cardiac cell types give rise to multiple new cells
during postnatal growth of the heart. Nonetheless, long-lived cardiomyocytes can
synthesize DNA after birth. In humans, postnatal cardiomyocytes can actually
produce DNA without nuclear division (polyploid nucleus). In addition to nuclear
diploidy and even sometimes polyploidy, a certain fraction (about 25%) of the
cardiomyocyte population undergoes a final nuclear division without cell division.
Bi-, tri-, and tetranucleated cells represent about 25.5, 0.4, and 0.1% of the
cardiomyocyte population [ 501 ].
Cardiomyocytes are able to partly repopulate human myocardium, but the
limited functional recovery after myocardial injury clearly demonstrates insufficient

11 Chondromodulin-1 is also called leukocyte-derived chemotaxin LeCT1.