Fiche publication
Date publication
juillet 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DE ARCANGELIS Adèle
Tous les auteurs :
Bouvard C, De Arcangelis A, Dizier B, Galy-Fauroux I, Fischer AM, Georges-Labouesse E, Helley D
Lien Pubmed
Résumé
AIMS: Integrins alpha6beta1 and alpha6beta4 are receptors for laminins, the main components of the basement membrane underlying the endothelial cells. In vitro, alpha6 integrin subunit (alpha6) 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 alpha6 in post-ischaemic vascular repair in vivo. METHODS AND RESULTS: We used the cre-lox system to generate a mouse line with specific alpha6 gene deletion in Tie2-lineage cells. In a model of hind-limb ischaemia, Tie2-dependent alpha6 deletion reduced neovessel formation and reperfusion of the ischaemic limb. Concerning the role for alpha6 in post-ischaemic vasculogenesis, we showed previously that alpha6 was required for EPC recruitment at the site of ischaemia. Here, we found that alpha6 deletion also reduced EPC mobilization from the bone marrow after ischaemia. Examination of the ischaemic muscles showed that Tie2-dependent alpha6 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 alpha6. To specifically investigate the role for alpha6 in angiogenesis, aortic rings were embedded in Matrigel or collagen and cultured ex vivo. In Matrigel, neovessel outgrowth from rings lacking alpha6 was strongly diminished, whereas no genotype-dependent difference occurred for rings in collagen. CONCLUSION: alpha6 plays a major role in both post-ischaemic angiogenesis and vasculogenesis.
Référence
Cardiovasc Res. 2012 Jul 1;95(1):39-47
