Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 724

11.5.7.1 Role of the Extracellular Matrix

Many factors associated with the extracellular matrix control angiogenesis [ 1185 ].
Matrix-sequestered growth factors support angiogenesis. Mechanical forces gener-
ated by endothelial cells and mainly myofibroblasts influence angiogenesis as well
as non-angiogenic translocation of the vasculature. Matricryptic sites are created by
peptidases on matrix constituents (fibronectin, collagens, vitronectin, and osteopon-
tin). They bind to cell integrins, hence priming signaling to moving endothelial cells.
Released matrikines 56 positively or negatively regulate angiogenesis (Sect. 10.5.2 ).
Matrix remodeling and vascular regression contribute to the inflammation-driven
angiogenesis as well as tissue repair. In the absence of vascular regression, positive
feedback between vessels and inflammatory infiltrate sustain the new vasculature
and exacerbate inflammation [ 1185 ]. Macrophages participate in pericyte apoptosis
and capillary regression. Peptidases MMP1 and MMP10 intervene in capillary
regression. Plasminogen and plasma kallikrein may also accelerate the process.

11.5.7.2 Angiopoietins

Among common regulators of angiogenesis and inflammation, angiopoietin-1 and -
2 (Ang1-Ang2) hinder and enhance inflammation, respectively [ 1286 ]. The Ang-
TIE2 pathway regulates vessel maturation and quiescence to stabilize newly formed
blood vessels. 57 Angiopoietin-1 is secreted by pericytes and activates TIE2 receptor
protein Tyr kinase (paracrine TIE2 activation). Angiopoietin-2 antagonizes the
anti-inflammatory effect of angiopoietin-1, as it enhances leukocyte extravasation.
Angiopoietin-2 released by endothelial cells is an antagonist for TIE2 (autocrine
TIE2 regulation) on vascular endothelial cells that destabilizes mature blood
vessels. 58 Angiopoietin-2 also acts as an agonist of TIE2 on lymphatic endothelial
cells. The quiescent endothelium is not affected by local perfusion of tumor-necrosis
factor- α , whereas tumor vasculature is disrupted [ 1287 ].

56 Peptides generated by proteolytic cleavage of constituents of the extracellular matrix that regulate
positively or negatively cell activities, similarly to cytokines or other types of regulatory peptides.
57 Stimulated TIE2 activates the PI3K-PKB pathway. Stimulated TIE2 interacts with ABIN2
adaptor and blocks NF B implicated in the synthesis of tissue factor as well as ICAM1 and

VCAM1 adhesion molecules expressed by adjoining endothelial cells.
58 Angiopoietin-2 sensitizes endothelium for TNF

κ

α

-mediated inflammation and upregulates adhe-
sion molecules ICAM1 and VCAM1 on endothelial cells.