Cell-autonomous requirement for β1 integrin in endothelial cell adhesion, migration and survival during angiogenesis in mice

Timothy R. Carlson, Huiqing Hu, Rickmer Braren, Yung Hae Kim, Rong A. Wang

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

131 Zitate (Scopus)

Abstract

β1 integrin (encoded by ltgb1) is established as a regulator of angiogenesis based upon the phenotypes of complete knockouts of β1 heterodimer partners or ligands and upon antibody inhibition studies in mice. Its direct function in endothelial cells (ECs) in vivo has not been determined because Itgb1-/- embryos die before vascular development. Excision of Itgb1 from ECs and a subset of hematopoietic cells, using Tie2-Cre, resulted in abnormal vascular development by embryonic day (e) 8.5 and lethality by e10.5. Tie1-Cre mediated a more restricted excision of Itgb1 from ECs and hematopoietic cells and resulted in embryonic lethal vascular defects by el1.5. Capillaries of the yolk sacs were disorganized, and the endothelium of major blood vessels and of the heart was frequently discontinuous in mutant embryos. We also found similar vascular morphogenesis defects characterized by EC disorganization in embryonic explants and isolated ECs. Itgb1-null ECs were deficient in adhesion and migration in a ligand-specific fashion, with impaired responses to laminin and collagens, but not to fibronectin. Deletion of Itgb1 reduced EC survival, but did not affect proliferation. Our findings demonstrate that β1 integrin is essential for EC adhesion, migration and survival during angiogenesis, and further validate that therapies targeting β1 integrins may effectively impair neovascularization.

OriginalspracheEnglisch
Seiten (von - bis)2193-2202
Seitenumfang10
FachzeitschriftDevelopment (Cambridge)
Jahrgang135
Ausgabenummer12
DOIs
PublikationsstatusVeröffentlicht - Juni 2008

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