ECM Remodeling in Angiogenesis - Mechanical and Chemical Signaling in Angiogenesis - page 183

Fig. 1 Schematic depiction
of the two different processes
by which new blood vessels
form in the body.
Vasculogenesis typically
occurs in development, with
angiogenesis occurring
throughout life. This chapter
focuses on how the ECM is
remodeled during the latter
process. (Figure reproduced
from [ 139 ] with permission
from Elsevier.)
environmental pH, mechanical stresses, tumor growth, or the presence of immune
or inflammatory cells. Soluble growth factors, such as vascular endothelial growth
factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth
factor (FGF), and hepatocyte growth factor (HGF), are potent pro-angiogenic
factors. Stabilizing immature vessels requires molecules such as angiopoietins-1
and -2, TGF-b, and sphyngosine-1 phosphate (S1-P), which are also considered
pro-angiogenic. On the other side of the balance, suppressive signals from
angiogenesis inhibitors include a-interferon, platelet factor-4, and thrombospon-
din-1, as well as other cryptic protein fragments [ 3 , 4 ]. Matrix metalloproteinases
(MMPs) and their endogenous inhibitors can also be considered in the context of
the angiogenic switch, as they function as both pro- and anti-angiogenic molecules
and are essential in each step of capillary formation and remodeling [ 5 ].
2 Changes in the ECM Accompany Each Stage
of Angiogenesis
During the initial stages of angiogenesis, contact between ECs and the ECM is a
key controller of angiogenic signaling. ECs must adhere to the ECM in order to
properly migrate, a necessary requirement for initiating angiogenic sprouting [ 6 ].
The ECM immobilizes angiogenic cytokines, and thus coordinates signals
transduced to ECs via both growth factor receptors and integrin cell adhesion