Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 274

A set of epithelial cells in the cardiac wall generate cardiac fibroblasts and
participate in coronary vasculogenesis. Another set interacts with myocardioblasts
for myocyte differentiation into cardiac Purkinje cells. Certain epicardium-derived
cells migrate in the core of the endocardial cushions to produce atrioventricular
valve leaflets. Epithelial-to-mesenchymal transformation occurs also in adult life,
especially in cardiovascular diseases such as atherosclerosis, intimal hyperplasia,
and aneurysms.
Ubiquitous periostin is involved in epithelial-mesenchymal transformation and
subsequent mesenchymal maturation, with differentiated mesenchyme and con-
densed matrix in embryonic heart valves. Periostin is also highly expressed in
the myocardium in patients with heart failure. Periostin inhibits cardiomyocyte
spreading and adhesion of cardiac fibroblasts [ 490 ].
During normal heart development, epicardial-derived cells (EPDC) undergo an
epithelial-mesenchymal transition in response to BMP, FGF, and TGF

released
from the myocardium (Vol. 2 - Chap. 3. Growth Factors). Secreted myocardial
thymosin-

β

4 then induces EPDC migration into the myocardium, where they
respond to angio- (VEGF and FGF2) or arteriogenic (PDGF and TGF

β

)growth
factors and differentiate into endothelial and smooth muscle cells, respectively,
leading to a capillary plexus and stabilizing coronary vessels.

β

6.1.4 Vasculo- and Angiogenesis

Embryonic coronary vessel development involves the activation and proliferation
of epicardial cells, followed by an epithelial-mesenchymal transition. Mural and
mesenchymal cell markers such as PDGFR are upregulated [ 491 ]. Signaling by

PDGF that causes the formation of stress fibers and loss of intercellular contacts of
epicardial cells is needed for epicardial cell proliferation.
Endothelium-lined tubes construct a functional circulatory network. The for-
mation of endothelial vacuoles followed by intra- and intercellular fusion drives
vascular lumen genesis [ 492 ]. These endothelial pinocytic vacuoles quickly occur,
fuse together, and enlarge to create the tube lumen. Endothelial cells form extensive
contacts between themselves and merge their intracellular vacuoles without cyto-
plasmic mixing. The vacuolar compartments in adjacent endothelial cells associate
and form a continuous lumen in developing blood vessels.
During embryogenesis, the generation of new cardiomyocytes from progenitor
cells and existing cardiomyocytes is associated with the development of the
coronary vasculature from progenitors that originate from the endothelium as well
as proepicardial organ and neural crest [ 493 ]. Coupling of myocardial and coronary
development is mediated by bone morphogenetic proteins and fibroblast (FGF) and
vascular endothelial (VEGFa) growth factors.
The myocardial development relies [ 493 ]: (1) in cardiomyocytes, on growth
factors and their receptors, such as VEGFa, BMPR1a (ALK3), FGFR1 and FGFR2;
MAPK14 (P38MAPK

β

α ), TxnRd2 thioredoxin reductase, and transcription factors