Vasculature Growth - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 614

10.5 Extracellular Matrix in Vessel Formation

Angiogenesis depends on many growth factors and enzymes, hence different cell
types and surrounding medium. The behavior of endothelial cells, especially their
migration and proliferation as well as formation of tubular structures is influenced
by the extracellular matrix (Table 10.5 ). Tip cells produce peptidases for cell
migration, such as membrane-type matrix metallopeptidase mt1MMP (or MMP14).
Nitric oxide, prostaglandin-E2, and CCL2 chemokine increase the cell-surface
clustering and activity of mt1MMP [ 1185 ].
Interactions between endothelial and surrounding cells, such as pericytes and
vascular smooth myocytes, regulate not only vessel stabilization and remodeling,
but also vascular formation. Intercellular communications are based on multiple
molecules, such as transforming growth factor- , angiopoietins, platelet-derived

growth factor, sphingosine 1-phosphate, and Notch ligands, among others [ 1186 ].
Cell shape is coupled to proliferation. Cell division depends more on the degree
of possible extension than the level of matrix binding. The actin cytoskeleton state
and activity of myosin contribute to cell and tissue growth. Laminin, fibronectin,
and collagen-1, -3, -4, and -5 promote cell spreading.
Rho GTPases are involved in tension-dependent growth control, because they
regulate cytoskeletal contractility. Matrix-associated cytoskeletal mechanics can
explain tension-driven tissue modeling. Podosomes of endothelial cells, sites of
MMP concentration, are involved in endothelial cell migration and angiogenesis.

β

10.5.1 Growth Factors

Many growth factors such as VEGF bind to matrix constituents.

Table 10.5. Sprout endothelial cells and inflammatory and angiogenic agents (Source: [ 1185 ];
VEGFR1 S : soluble VEGFR1). A nascent vascular sprout contains 3 types of endothelial cells. Tip
cells produce VEGFR2, VEGFR3, DLL4, and angiomotin, among others, and navigate into the
surrounding tissue, but proliferate poorly. Stalk and phalanx cells form the lumen and promote
nascent vessel stabilization.

Type Stimulators

Tip VEGF, S1P,

Bdk, TNF

α

EGFL7, FGF, VEGF, VEGFR1 S Stalk

Phalanx Ang2, BMP9, FGF2, VEGF,

Tsp