Biomedical Engineering Reference
In-Depth Information
Platelet-derived growth factor
primes phosphorylation of signaling proteins,
such as the PDGF receptor and phospholipase-C
1, via intracellular production
of H
2
O
2
in particular. Factor PDGF is especially involved in smooth myocyte
proliferation and migration during vascular remodeling.
The
peroxiredoxin-2
(Prx2), a peroxidase that eliminates endogenous H
2
O
2
in
response to growth factor signaling, is a negative regulator of PDGF signaling,
especially during vascular remodeling [
1496
]. Neointimal layers of injured carotid
arteries of mice lacking Prx2 are thicker than those of wild-type mice. Prx2
is involved in PDGF-dependent neointimal thickening, atherosclerosis, and other
lesions of blood vessels.
Urokinase (uPA), involved in smooth myocyte behavior (proliferation, adhesion,
and migration)
77
participates in wall remodeling via the uPA receptor (uPAR).
Activated uPAR associates with PDGFR
γ
receptor,
78
β
hence leading to PDGF-
independent PDGFR
activation of its protein Tyr kinase activity [
1497
].
The expression of P2X
4
receptors in the vessel wall strongly increases after
balloon injury, with a much higher density in the media, a very high density in the
enlarged neointima, and a ten-time density increase in the endothelium [
1498
]. Acti-
vated P2X
4
receptors can thus be involved in neointimal proliferation. Examinations
of blood vessels used for coronary artery grafts show that levels of P2X
4
are much
lower in arterial vessels than vein samples. Therefore, artery grafts are more suitable
than venous grafts to prevent restenosis and atheroma. P2Y
2
Expression also
increases in balloon-injured endothelium and neointima, but without discernible
differences between different examined vessel types.
In a dynamical adaptation model of the vessel wall under hypertension, the
time evolution of the vessel geometry (external
β
χ
i
perimeters, wall
thickness
h
, vessel length
L
) has been described, assuming a thick-walled tube made
of non-linear elastic incompressible material [
1499
]. The geometrical quantities
are expressed as functions of the respective stresses in normal (superscript n) and
hypertensive (superscript h) states. For example, the remodeling rate equation of the
wall thickness is given by:
χ
e
and internal
c
h
c
h
c
n
dh
/
dt
=(
1
/
τ
h
)[(
θ
(
t
)
−
θ
)
/
θ
]
,
(11.9)
where
τ
h
is the corresponding time constant and
c
θ
the wall-averaged circumfer-
ential stress. In particular, the model predicts that the vessel caliber increases up
to a maximum and, then, decreases to a limit value 1 month later. The mechanical
properties vary during the remodeling. The constitutive equations must then include
77
Migration
of
smooth
myocytes
involves
activation
of
TyK2
kinase,
phosphatidylinositol
3-kinase, and the RoCK pathway.
78
The 2 receptors PDGFR
α
and PDGFR
β
are expressed in smooth myocytes, but PDGFR
β
expression is stronger. Receptor uPAR interacts also with integrins, LDL receptor-related proteins,
G-protein-coupled receptor formyl peptide receptor (FPRL1, or lipoxin A4 receptor LXa4R),
FGF1 receptor.
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