Vasculature Growth - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 644

Fig. 10.3 Angiopoietins are
involved in angiogenesis and
inflammation. They have
antagonist actions
(Source: [ 1286 , 1287 ]).

macrophage

TNF α

inflammation

TNFR

EC

NFκΒ

ICAM1

PKB

VCAM1

ABIN2

PI3K

Ang2

Tie2

pericyte

Ang1

Angiopoietin-1

Angiopoietin-1 is expressed by vascular smooth myocytes and pericytes, as well
as fibroblasts and several types of non-vascular cells, whereas angiopoietin-2 is
primarily produced by endothelial cells.
Angiopoietin-1 regulates blood vessel maturation [ 1288 ]. During the maturation
stage of blood vessel formation, endothelial cells that form the channel recruit
supporting mural cells (pericytes and smooth myocytes) by releasing PDGFbb
dimer. Mural cells subsequently adhere to endothelial cells to build stable blood
vessels, as they stimulate TIE2 receptor. Paracrine angiopoietin-1 produced by
mural cells stabilizes newly formed blood vessels and decreases vascular perme-
ability. The Ang1-TIE2 pathway indeed favors the association of pericytes with
endothelial cells to reduce vascular leakage. Angiopoietin-1 tightens blood vessels
via adhesions between cells as well as between cells and the extracellular matrix.
Angiopoietin-1 induces formation of TIE2 clusters in quiescent endothelial
cells at intercellular junctions to transduce survival signals [ 1289 ]. Receptor TIE2
activation primes several signaling pathways. The dominant pathway corresponds
to the PI3K-PKB survival axis.
During angiogenesis, blood vessels change their caliber to adapt to the nutritional
needs of tissues. The Ang1-TIE2 complex regulates the widening of blood vessels.
Angiopoietin-1 has anti-inflammatory and vascular permeability-inhibiting
effects via sphingosine kinase-1 that catalyzes the formation of sphingosine
1-phosphate [ 1289 ]. Angiopoietin-1 collaborates with VEGF during blood and
lymph vessel development.
Ligand-bound TIE2 leads to its phosphorylation and recruitment of adaptor
proteins to activate different signaling pathways. Ang1-TIE2 complexes associate