TY - JOUR
T1 - Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis
AU - Carmeliet, Peter
AU - Lampugnani, Maria Grazia
AU - Moons, Lieve
AU - Breviario, Ferrucio
AU - Compernolle, Veerle
AU - Bono, Françoise
AU - Balconi, Giovanna
AU - Spagnuolo, Raffaella
AU - Oosthuyse, Bert
AU - Dewerchin, Mieke
AU - Zanetti, Adriana
AU - Angellilo, Anne
AU - Mattot, Virginie
AU - Nuyens, Dieter
AU - Lutgens, Esther
AU - Clotman, Frederic
AU - De Ruiter, Marco C.
AU - Groot, Adriana Gittenberger De
AU - Poelmann, Rob
AU - Lupu, Florea
AU - Herbert, Jean Marc
AU - Collen, Désiré
AU - Dejana, Elizabetta
N1 - Funding Information:
The authors thank Dr. K. Alitalo for VEGF-C, Dr. S. Soddu for p53 −/− mice, Dr. P. G. Pelicci for p21 −/− mice, Dr. S. Citi for cingulin antibodies, Dr. P. Lonai for pgk:Cre mice, Dr. D. Hicklin and P. Bohlen (Imclone System, Inc.) for support. This work was supported by Associazione Italiana per la Ricerca sul Cancro, the European Community (Biomed BMH4-CT98–3380), Actie Levenslijn (#7.0019.98), and the Italian National Research Council (CNR 97.01299.PF49). M. G. L. is a recipient of a NATO travel grant.
PY - 1999/7/23
Y1 - 1999/7/23
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(00)81010-7
DO - 10.1016/S0092-8674(00)81010-7
M3 - Article
C2 - 10428027
AN - SCOPUS:0033597718
SN - 0092-8674
VL - 98
SP - 147
EP - 157
JO - Cell
JF - Cell
IS - 2
ER -