Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 471

9.4 Endothelial Cell Migration

Endothelial cells migrate during angiogenesis (Chap. 10 ; Vol. 2 - Chap. 6.
Cell Motility). Chemokines of the CXC set enhance the migratory capacity of
endothelial cells and facilitate homing of endothelial progenitor cells into ischemic
tissues. Chemokine ligand CXCL12 25 promotes tubulogenesis of microvascular
endothelial cells via enhanced expression of growth factors VEGF and FGF2.
Hypoxia-inducible factor HIF1 primes CXCL12 synthesis in ischemic tissue for
cell recruitment and homing, especially of vascular endothelial cells and circulating
progenitor cells that express chemokine CXCR4 receptor, 26 thereby boosting tissue
regeneration.
Chemokine CXCL12 activates the PKB-NOS3 axis as well as mitogen-activated
protein kinases, such as ERK1 and ERK2, JNK, and P38MAPK, in different cell
types. Activated nitric oxide synthase NOS3 then produces nitric oxide that sub-
sequently nitrosylates (inactivates) mitogen-activated protein kinase phosphatase
MKP7. Phosphatase MKP7 then cannot inhibit Jun N-terminal kinase JNK3 that
binds to its adaptor

-arrestin-2 [ 874 ]. 27 In bovine aortic endothelial cells, CXCL12
activates an NOS3-independent pathway that targets ERK1 and ERK2 to initiate cell
migration.

β

9.5 Molecular Expression in the Vascular Endothelium

The vascular endothelium synthesizes numerous molecules to regulate its behavior
and to respond to environmental cues, as well as to control its surrounding
(Table 9.6 ,Fig. 9.2 ).
Vascular endothelial cells, like vascular smooth myocytes, possess enzymes of
the cytochrome-P450 superfamily, such as epoxygenases and

-hydroxylases that
metabolize arachidonic acid released from phospholipids of the plasma membrane
by activated phospholipase-A2 into vasoactive substances.
20-Hydroxyeicosatetraenoic acid (20HETE) is produced by cytochrome-P450 in
vascular smooth myocytes as well as uniquely in endothelial cells of pulmonary
arteries. Compound 20HETE enhances reactive oxygen species production by

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primitive hematopoietic progenitors share markers such as VEGFR1, VEGFR2, TIE2, PECAM1,
type-1 membrane glycoproteic endoglin (or CD105), and cadherin-5 with endothelial cells.
25 A.k.a. stromal cell-derived factor SDF1. It is produced in 2 forms by alternative splicing of the
same Cxcl12 gene transcript: SDF1 α (or CXCL12a) and SDF1 β (or CXCL12b).

26 A.k.a. Fusin or leukocyte-expressed

7-transmembrane-domain receptor (LESTR). With its

coreceptor CXCR7, it is required for vascular development.
27 Activity of JNK1 is also suppressed after nitrosylation (Cys116) by nitric oxide.