title: Tie2-dependent knockout of α6 integrin subunit in mice reduces post-ischaemic angiogenesis.
abstract: OBJECTIVE
  Integrins α6β1 and α6β4 are receptors for laminins, the main components of the basement membrane underlying the endothelial cells. In vitro, α6 integrin subunit (α6) expression at the surface of endothelial cells and their progenitors (EPCs) is up-regulated by pro-angiogenic growth factors and is crucial for adhesion, migration, and pseudotube formation. We investigated the role for α6 in post-ischaemic vascular repair in vivo.
  
  
  RESULTS
  We used the cre-lox system to generate a mouse line with specific α6 gene deletion in Tie2-lineage cells. In a model of hind-limb ischaemia, Tie2-dependent α6 deletion reduced neovessel formation and reperfusion of the ischaemic limb. Concerning the role for α6 in post-ischaemic vasculogenesis, we showed previously that α6 was required for EPC recruitment at the site of ischaemia. Here, we found that α6 deletion also reduced EPC mobilization from the bone marrow after ischaemia. Examination of the ischaemic muscles showed that Tie2-dependent α6 deletion decreased the recruitment of pro-angiogenic Tie2-expressing macrophages. In the Matrigel plug assay, fibroblast growth factor-2-induced vascularization was diminished in mice lacking endothelial α6. To specifically investigate the role for α6 in angiogenesis, aortic rings were embedded in Matrigel or collagen and cultured ex vivo. In Matrigel, neovessel outgrowth from rings lacking α6 was strongly diminished, whereas no genotype-dependent difference occurred for rings in collagen.
  
  
  CONCLUSIONS
  α6 plays a major role in both post-ischaemic angiogenesis and vasculogenesis.
authors.affiliation: INSERM U765, Faculté des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l'Observatoire, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Bouvard
authors.forename: Adèle
authors.initials: A
authors.lastname: De Arcangelis
authors.forename: Blandine
authors.initials: B
authors.lastname: Dizier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Galy-Fauroux
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Fischer
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Georges-Labouesse
authors.forename: Dominique
authors.initials: D
authors.lastname: Helley
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002465:Cell Movement; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D039503:Integrin alpha6 / Q000502:physiology*; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D021122:Protein Subunits / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D042787:Receptor, TIE-2
chemical_list: D039503:Integrin alpha6; D021122:Protein Subunits; D016222:Fibroblast Growth Factor 2; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse