Vasculature Growth - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 615

10.5.1.1 VEGF

Vascular endothelial growth factors connected to matrix constituents can be cleaved.
A C-terminus of variable length according to the involved peptidase is then released.
Released VEGF from matrix stores promotes angiogenesis.
Various VEGF isoforms have different affinities for given matrix proteins.
However, soluble VEGF subtypes (VEGF S ) lack the matrix-binding region. They
are either secreted as short alternative spliced forms such as VEGF 120 or cleaved
by plasmin or matrix metallopeptidases, such as MMP3, MMP7, MMP9 (in the
presence of heparin), and MMP19 isozymes.
Matrix-bound and soluble VEGFs can both trigger VEGFR phosphorylation, but
differ in signaling. Matrix anchorage leads to clustering of VEGFR2, promotes
receptor endocytosis, and raises downstream phosphorylation kinetics. Soluble
VEGF has a tendency to build low-density, poorly branched vascular networks
(vascular hyperplasia) [ 1185 ]. On the other hand, matrix-bound VEGF favors highly
branched vessels.

10.5.1.2 FGF

Fibroblast growth factors interact with matrix proteins, particularly heparan sulfate
proteoglycans. The extracellular matrix contributes to the regulation of FGF
signaling. In pancreatic β cells, FGFR1 concentration is reduced by the binding

of α 6 -integrin to laminin [ 1185 ].

10.5.1.3 PDGF

Platelet-derived growth factor can link to several collagen types, laminin-1, nidogen,
and perlecan. Binding to matrix constituents may serve for storage in cell's
surrounding for later release and signaling.

10.5.1.4 TGF

β

Transforming growth factor- can anchor to the extracellular matrix. This anchor-

age can contribute to its activation. Thrombospodin binding stimulates TGF

β

,but

thrombospodin-1 inhibits VEGF factor.