Vasculature Growth - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 619

molecules [ 1192 ]. This cell adhesion molecule is involved in angiogenesis once
PECAMs are linked, and also in mechanical stress sensing and its anti-apoptotic
function.

10.5.3.1 Integrins

Integrins are implicated as mediators of vascular formation and homeostasis, due
to their role in cell adhesion, migration, positioning, proliferation, and differen-
tiation [ 1193 ]. Endothelial cells express different vascular integrins involved in
vasculo- and angiogenesis such as

α V β 3 -integrins.
Plasmalemmal integrins that interact with the extracellular matrix promote
cell attachment to the extracellular matrix and transduce signals to the nucleus.
Integrin-mediated adhesion to the extracellular matrix activates the ERK pathway.
Activated extracellular signal-regulated kinases stimulate cyclin-D1. Cell division is
controlled by cyclins, cyclin-dependent kinases, and CDK-inhibitors [ 1194 ](Vol.2-
Chap. 2. Cell Growth and Proliferation).
Integrins are also required in VEGF signaling via Ras GTPase or phosphati-
dylinositol 3-kinase. Integrin-binding protein lactadherin 24 is involved in VEGF-
dependent neovascularization [ 1195 ]. Lactadherin interacts with

α V β 5 -
integrins and alters VEGF-dependent PKB phosphorylation and neovascularization.
Activated

α V β 3 -and

α V β 3 -integrin supports angiogenesis and growth of brain metastasis
via upregulation of vascular endothelial growth factor under normoxic condi-
tions [ 1196 ]. Synthesis of VEGF is post-transcriptionally controlled by phosphory-
lation (inhibition) of translational repressor 4E-binding 4eBP1 protein.

10.5.3.2 Tenascins

The tenascin (Ten) family of matrix, cell adhesion glycoproteins (Table 10.9 )
contributes to vasculogenesis and various normal and pathological processes of
mature life, such as wound healing and vascular diseases [ 1197 ].
In association with matrix proteins and plasmalemmal receptors such as in-
tegrins, tenascins have opposite cellular functions, according to the mode of
presentation, cell type, and differentiation state of the target tissues. Tenascins are
regulated by growth factors, vasoactive peptides, matrix proteins, and mechanical
factors [ 1197 ].
Tenascin-C interacts with integrins, collagens, proteoglycans, and fibronectin.
It behaves either as an adhesive or anti-adhesive protein. It binds to annexin-2, a
plasmalemmal receptor of endothelial cells [ 1198 ]. The TENC gene expression is
mechanosensitive.

24 Lactadherin is also known as milk fat globule-EGF factor-8 (MFGE8).