Vasculature Growth - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 603

from pre-existing vessels. Angiogenesis includes sequential events: (1) increased
capillary permeability and endothelial cell and pericyte activation and hypertrophy;
(2) destabilization with degradation of the vascular basement membrane and remod-
eling of the extracellular matrix; (3) endothelial cell proliferation and migration
in the target extracellular matrix; (4) capillary lumenogenesis (Sect. 10.2.5 ); and
(5) maturation with recruitment of pericytes, subsequent inhibition of endothelial
proliferation, basement membrane reconstitution, and junctional complex forma-
tion, that stabilizes new vessels. Bone marrow-derived pericytes are also recruited
for angiogenesis, particularly after ischemia [ 1168 ]. Angioblasts are able to differ-
entiate into both blood and endothelial cells.
Both chemotaxis and haptotaxis 2 contribute to tissue development, defense, and
repair. Various fibronectin-binding integrin types collaborate to yield cell adhesion
and migration on fibronectin [ 1164 ]. In addition, disruption of epithelial layers
instantaneously generates lateral electric fields [ 1165 ], directed toward the wound
center, with sustained outward electric currents. The lesion shunts the transepithelial
potential difference. These electric fields trigger cell migration during wound
healing. Electrotaxis is controlled by PI3K c1γ and PTen phosphatase [ 1166 ].
Vascular sprouts develop and build a structure. Angiogenesis is tightly coupled
to tissue development to supply the growing tissue with oxygen and nutrients
and remove its metabolic waste. The three-dimensional, fractal-like network of
branched vessels results from local growth gradients over small distances. Localized
production of growth factors promotes tissue expansion and determination of the
position of branching nodes. The process is adaptive, because vessel development,
maturation, and regression coexist. Local control of cell responses to stimuli, such
as the regulation of the extracellular matrix, avoids disorganization.
Angiogenic vessels differ from mature vessels. The wall structure is not well
organized. The interactions between endothelial cells and pericytes are impaired.
The wall is leaky. Angiogenic endothelial cells have altered surface markers and
adhesion molecules.
Vessel maturation leads to a fully formed and functional network. After sup-
pression of endothelial proliferation and sprouting, mural cells are incorporated
into vessel walls and structural elements are constructed (valves, fenestrations or,
conversely, tight junctions, etc.).

10.2.1 Stem, Progenitor, and Precursor Cells in Angiogenesis

and Neovascularization

Fetal cells (trophoblasts, erythroblasts, leukocytes, hematopoietic progenitors, and
mesenchymal stem cells) migrate in the maternal circulation during pregnancy.

2 Haptotaxis corresponds to the adhesion gradient associated with the concentration of the
constituents of the support medium, i.e., gradient in extracellular matrix density.