Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis

Citation
P. Carmeliet et al., Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis, CELL, 98(2), 1999, pp. 147-157
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL
ISSN journal
0092-8674 → ACNP
Volume
98
Issue
2
Year of publication
1999
Pages
147 - 157
Database
ISI
SICI code
0092-8674(19990723)98:2<147:TDOCTO>2.0.ZU;2-K
Abstract
Vascular endothelial cadherin, VE-cadherin, mediates adhesion between endot helial cells and may affect vascular morphogenesis via intracellular signal ing, but the nature of these signals remains unknown. Here, targeted inacti vation (VEC-/-) or truncation of the beta-catenin-binding cytosolic domain (VECdelta C/delta C) Of the VE-cadherin gene was found not to affect assemb ly of endothelial cells in vascular plexi, but to impair their subsequent r emodeling and maturation, causing lethality at 9.5 days of gestation. Defic iency or truncation of VE-cadherin induced endothelial apoptosis and abolis hed transmission of the endothelial survival signal by VEGF-A to Akt kinase and Bc12 via reduced complex formation with VEGF receptor-2, beta-catenin, and phosphoinositide 3 (PI3)-kinase. Thus, VE-cadherin/beta-catenin signal ing controls endothelial survival.