Vasculature Growth - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 641

10.6.5.2 Transforming Growth Factor- β

Nascent channels become covered not only by endothelial cells, but also by
pericytes and vascular smooth muscles. Pericytes and smooth myocytes stabilize
small and large blood vessels, respectively. Pericytes differentiate from perivascular
progenitor cells in the bone marrow. The differentiation of progenitors into pericytes
and vascular smooth myocytes is promoted by transforming growth factor-

β 1.

However, the latter can lead to local destabilization and regression.

10.6.5.3 Platelet-Derived Growth Factors

Vascular endothelial and platelet-derived growth factors contribute to angiogenesis
and vessel stabilization by activating vascular endothelial and smooth muscle
cells, respectively. At an optimal angiogenic dose, PDGFbb homodimer or VEGF
alone promotes angiogenesis. During PDGF-VEGF costimulation, VEGF and
PDGF have antagonistic effects on angiogenesis. Vascular endothelial growth factor
receptor-2 actually binds to and antagonizes platelet-derived growth factor receptor-
β in mural cells to prevent pericyte recruitment to nascent vessels and limit

neovascularization [ 1278 ].
Homodimer PDGFbb and angiopoietin-1 recruit mural cells around endothelial
tubes. Protomer PDGFb on the endothelial cell surface ensures suitable coverage
of blood vessels by pericytes in the microcirculation and smooth myocytes in
the macrocirculation. Factor PDGFb is needed for recruitment of pericytes and
maturation of the microvasculature. The PDGFa-PDGFR α pair recruit angiogenic

stromal fibroblasts [ 1279 ].
Homodimer PDGFcc is secreted and then processed to bind its receptor. 59 It
causes monocyte migration and upregulates expression of matrix metallopeptidases
MMP2 and MMP9. It operates on multiple cell types, such as vascular endothelial
and other mural cells, macrophages, as well as choroidal fibroblasts and retinal
pigment epithelial cells [ 1280 ]. 60 In addition, PDGFcc possesses many molecular
angiogenic targets, such as PDGFbb factor and PDGFR

receptors, and provokes
phosphorylation (inactivation) of glycogen synthase kinase GSK3

α

by protein
kinase-B. The latter, once activated, impedes PDGFcc-induced angiogenesis [ 1280 ].

β

59 Platelet-derived growth factors form dimers that bind and activate their receptor tyrosine kinases
PDGFR that also build dimers. Both PDGFc and PDGFd are produced as

latent growth factors that require proteolytic removal of their N-terminal CUB (complement
subcomponents C1r and C1s, fibropellin-1, or uEGF, from Strongylocentrotus purpuratus (Purple
sea urchin), and bone morphogenetic protein BMP1) domain to become active.
60 Platelet-derived growth factors PDGFaa, PDGFab, PDGFbb, and PDGFcc activate PDGFR αα
homodimers, PDGFbb and PDGFdd stimulate PDGFR

α and PDGFR β

ββ

homodimers, and PDGFab, PDGFbb,

αβ

PDGFcc, and PDGFdd activate PDGFR heterodimers.