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

Peter Carmeliet, Maria Grazia Lampugnani, Lieve Moons, Ferrucio Breviario, Veerle Compernolle, Françoise Bono, Giovanna Balconi, Raffaella Spagnuolo, Bert Oosthuyse, Mieke Dewerchin, Adriana Zanetti, Anne Angellilo, Virginie Mattot, Dieter Nuyens, Esther Lutgens, Frederic Clotman, Marco C. De Ruiter, Adriana Gittenberger De Groot, Rob Poelmann, Florea LupuJean Marc Herbert, Désiré Collen, Elizabetta Dejana

Research output: Contribution to journalArticlepeer-review

Abstract

Vascular endothelial cadherin, VE-cadherin, mediates adhesion between endothelial cells and may affect vascular morphogenesis via intracellular signaling, but the nature of these signals remains unknown. Here, targeted inactivation (VEC(-/-)) or truncation of the β-catenin-binding cytosolic domain (VEC(δc/δc)) of the VE-cadherin gene was found not to affect assembly of endothelial cells in vascular plexi, but to impair their subsequent remodeling and maturation, causing lethality at 9.5 days of gestation. Deficiency or truncation of VE-cadherin induced endothelial apoptosis and abolished transmission of the endothelial survival signal by VEGF-A to Akt kinase and Bcl2 via reduced complex formation with VEGF receptor-2, β-catenin, and phosphoinositide 3 (PI3)-kinase. Thus, VE- cadherin/β-catenin signaling controls endothelial survival.

Original languageEnglish (US)
Pages (from-to)147-157
Number of pages11
JournalCell
Volume98
Issue number2
DOIs
StatePublished - Jul 23 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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