Biomedical Engineering Reference
In-Depth Information
10.2.4
Other Modes of Vessel Formation and Remodeling
Changes in the local balance between pro- and anti-angiogenic factors can lead to
the elimination of new connections (
pruning
). The splitting of vessels through the
insertion of tissue pillars (
intussusception
) expends the vascular network.
Intussusception (“growth within itself”), a non-sprouting angiogenesis, repre-
sents a particular way of expanding and modifying a vessel network, as it creates
and remodels blood vessels via the formation of transluminal pillars [
1176
].
6
Regions of locally changed stress sensed by endothelial cells can trigger growth
of septa, ridges, pillars, and folds. Intussusception predominantly occurs in regions
with accelerated blood flow. Intussusceptive vascular growth and remodeling are
regulated by vascular growth factors, such as VEGF, PDGFb, and angiopoietins,
and TIE receptors.
Maturation is related to the transition from a growing vascular bed to a functional
network, characterized by stabilized vessels with mural cells and a basement
membrane, valved veins, capillaries, and lymphatics with either fenestrations or
tight junctions.
Perfusion reduces hypoxia-induced angiogenic factors and promotes vessel
maturation. Bone marrow-derived circulating cells can be retained in the perivas-
cular space due to CXCL12 chemokine in response to VEGFa and then enhance
endothelial proliferation.
6
Intussusception corresponds to pillar formation for capillary genesis. It is observed in the rapidly
expanding postnatal lung capillary bed. The shape of these pillars is maintained by endothelial
cells and pericytes. The pillars can grow in size and number. They can also merge to form
folds and new vascular branches. There are 3 modes of intussusception [
1176
]: intussusceptive
microvascular growth, arborization, and branching remodeling. Intussusceptive microvascular
growth is characterized by insertion of transluminal pillars, which induces a rapid expansion of the
capillary plexus. Vessels are generated from the capillary plexus by intussusceptive arborization
by perpendicular pillar formation in rows, which delineate future vessels. Pillar reshaping and
fusions determine the new vascular entity. Pillars and folds are then formed in the capillary sheet,
which separate the new vessels from the old capillary plexus. Intussusceptive branching remodeling
adapts the branching angle and the bores of the branches of new supplying and draining vessels
by insertion of transluminal pillars at branching points (abundant small holes are observed at
branching sites). The combined cross-sectional area of the branches is greater than that of the
stem: R
t
=
R
b
1
+
R
b
2
(subscripts
t
and
b
for trunk and branch) with 2
<
p
<
4,
p
depending both
on the trunk bore and the vessel type (supplying or draining). The area ratio is indeed significantly
different in arteries and veins [
1176
]. The distribution of blood flow at each bifurcation depends on
the asymmetry ratio between the two branches. Strong asymmetry can lead to vascular pruning
(non-perfusion and removal of branches at bifurcations). The time needed to complete pillar
formation ranges from 40 to 120 mn.
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