Biomedical Engineering Reference
In-Depth Information
promoting KLF2 expression. Factor KLF2 prevents VCAM1 synthesis, hence
leukocyte adhesion. Therefore, VCAM1 expression depends on the modulation rate
of the periodic flow [
927
].
9.5.9
Growth Factors and Regulators of Growth Factor
Signaling
Endothelial cells synthesize a huge number of factors (Tables
9.14
)to
9.18
).
They release numerous paracrine growth factors, also called
angiocrine factors
.
In fact, angiocrine factors comprise secreted molecules as well as plasmalemmal and
membrane-anchored compounds that are cleaved and generate liberated variants.
Some angiocrine factors can act on stem and progenitor cells, as endothelial
cells achieve an instructive vascular niche. Endothelial cells are indeed involved
in self-renewal of hematopoietic stem cells. Specific angiocrine factors produced
by endothelial cells in response to different stimuli either support self-renewal
and proliferation using the TOR-PKB pathway or, due to MAPK coactivation,
lineage-specific differentiation of hematopoietic stem and progenitor cells [
929
].
In particular, Notch ligands by endothelial cells promote HSC proliferation.
Angiocrine factors secreted from endothelium also regulate tumor cell prolifera-
tion and motility. Angiocrine factor Slit-2, which is inhibited by endothelial EPHa2
receptor, represses tumor growth.
Endothelial cells from different compartments of the vasculature, such as
arteries, veins, microcirculation segments, and lymphatic vessels, differ in their gene
expression patterns (different phenotypes). In addition, tumor endothelial cells also
differ by expression of specific markers.
9.5.9.1
Connective Tissue Growth Factor
Connective tissue growth factor production in endothelial cells can be induced by
bioactive lipids, such as lysophosphatidic acid and sphingosine 1-phosphate, and
platelets [
930
].
9.5.9.2
VEGF and Cadherin-5
Endothelial cells produce vascular endothelial (VE)-cadherin, or Cdh5, that binds
to cortical partners, such as
β
δ
γ
-catenin. Endothelial-specific cadherin-5
clusters build homotypic adherens junctions that enable endothelium stabilization,
as they prevent cell growth, proliferation, and apoptosis.
-,
1-, and
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