Vessel Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 348

This arterial apparatus afterward matures and sustains an asymmetrical remodeling.
The left fourth and sixth arch arteries persist and generate the aortic arch and
pulmonary trunk, whereas the right fourth and sixth branchial arch arteries regress,
as blood predominantly flows through the left arch arteries.
This event is concomitant with increased expression of growth factors, such as
platelet-derived (PDGF) and vascular endothelial (VEGF) growth factors. It follows
rotation and realignment of the ventricular outflow tract that forms part of the left
and right ventricles. Outflow tract rotation is required for reshaping of the right sixth
arch artery into a long, narrow vessel with reduced blood flow.
The transcription factor pituitary paired-like homeodomain-containing protein
Pitx2 (encoded by the homeobox PITX2 gene) stimulated by Nodal, a member
of the TGF growth factor superfamily involved in cell differentiation, mesoderm

formation, and subsequent organization of left-right axial structures, regulates the
asymmetric growth. It abounds in cells of the secondary heart field that includes
the myocardium of the left wall of the outflow tract. Pitx2

β

cells participate to the
control of rotation of the outflow tract. Factor Pitx2 is not synthesized in cell types
that belongs to or surrounds sixth branchial arch arteries [ 652 ]. Although branchial
arch artery remodeling requires Pitx2, it is not directly governed by Pitx2

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cells.
The anterior heart also requires FGF8 that is overexpressed in the absence of Pitx2
protein. Factor FGF8 may be involved in arch artery maturation. Besides, the Nodal-
Pitx2 pathway and abnormal rotation of the outflow tract do not strongly affect
branchial arch artery laterality.
Vascular growth factors, such as PDGFa protomer and VEGF, contribute to
branchial arch artery apparatus remodeling, as their inhibition specifically yields
loss of both left and right sixth arch arteries [ 652 ]. Expression of PDGFa is main-
tained on the left side but decays on the right. The concentration of phosphorylated
VEGFR2 in endothelial cells also decreases in the right sixth branchial arch artery,
whereas in the case of Pitx2 loss, PDGFa and VEGFR2 P levels remain symmetrical.
In addition, ligated left sixth branchial arch artery in 11.5-day-old mouse embryos
(before the onset of remodeling; i.e., approximately 35-day-old human embryos)
leads to their regression and development of right arteries [ 652 ]. In 4 among
6 embryos with ligated left sixth branchial arch artery, PDGFR and VEGFR2 P
signalings are reduced on the left side and maintained on the right side. Therefore,
hemodynamical stress shapes the asymmetrical arterial system by operating via
growth factors.

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7.3 Wall Structure

As blood pulses in an artery, its wall alternatively stretches and recoils. In 1733,
S. Hales described blood systolic storage and diastolic restitution. In 1899, O. Frank
modeled arterial capacitance by a windkessel element, i.e., a damping air chamber
incorporated in a rigid pipe network. Blood vessels are pressure and volume buffers.