Vasculature Growth - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 642

in pericytes and smooth myocytes is
required for guided migration and incorporation into the vessel wall, then cell
proliferation and maturation of the vasculature. Receptor PDGFR

Platelet-derived growth factor receptor- β

can cooperate
with G-protein-coupled receptors S1PRs, as sphingosine 1-phosphate is secreted by
endothelial cells to get the appropriate number of mural cells and form adhesion
sites between them and endothelial cells. Perivascular progenitors expressing
PDGFR

β

are recruited from the bone marrow to perivascular sites, particularly in
tumors [ 1281 ]. 61

β

10.6.5.4 Fibroblast Growth Factors

The initiation of angiogenesis particularly requires fibroblast growth factor-2 and
paracrine vascular endothelial growth factor. Growth factor activity that favors
either cell survival or apoptosis depends on activated signaling pathway. Both
VEGF and FGF2, independently of VEGF, are survival factors for endothelial cells,
whereas TGF

1 that acts via SMADs and MAPKs induces transient endothelial
cell apoptosis. 62

β

Growth factors FGF2, TGF β 1, and VEGF are often coexpressed

in tissues in which angiogeness occurs.

10.6.5.5 Prokineticins

Prokineticins Prok1 and Prok2 are mitogens for endothelial cells which bind to
cognate G-protein-coupled receptors PKR1 and PKR2. Prokineticin-2 is upregu-
lated in the bone marrow by CSF3 colony-stimulating factor. They promote both
angiogenesis and myeloid cell mobilization from the bone marrow [ 1282 ].

10.6.5.6 Midkine

Hypoxia increases midkine synthesis in human neutrophils, monocytes, M2 macro-
phages, and endothelial cells, as well as cancer cells [ 1283 ]. Midkine is a member
of the family of heparin-binding growth factors with pleiotrophin. Its production
results from binding of hypoxia inducible factor-1

to a hypoxia response element
in the midkine gene promoter. Midkine causes angiogenesis during ischemia.

α

61 During tumoral angiogenesis, pericytes have morphological abnormalities.
62 The transient apoptotic effect on endothelial cells of TGF

β

1 is followed by refractoriness of

β

these cells to TGF 1-induced apoptosis.