title: Alteration of developmental and pathological retinal angiogenesis in angptl4-deficient mice.
abstract: Proper vessel maturation, remodeling of endothelial junctions, and recruitment of perivascular cells is crucial for establishing and maintaining vessel functions. In proliferative retinopathies, hypoxia-induced angiogenesis is associated with disruption of the vascular barrier, edema, and vision loss. Therefore, identifying factors that regulate vascular maturation is critical to target pathological angiogenesis. Given the conflicting role of angiopoietin-like-4 (ANGPTL4) reported in the current literature using gain of function systems both in vitro and in vivo, the goal of this study was to characterize angiogenesis, focusing on perinatal retinal vascularization and pathological circumstances in angpl4-deficient mice. We report altered organization of endothelial junctions and pericyte coverage, both leading to impaired angiogenesis and increased vascular leakage that were eventually caught up, suggesting a delay in vessel maturation. In a model of oxygen-induced retinopathy, pathological neovascularization, which results from tissue hypoxia, was also strongly inhibited in angptl4-deficient mice. This study therefore shows that ANGPTL4 tunes endothelial cell junction organization and pericyte coverage and controls vascular permeability and angiogenesis, both during development and in pathological conditions.
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology, Paris 75005, France.
authors.forename: Elisa Gomez
authors.initials: EG
authors.lastname: Perdiguero
authors.forename: Ariane
authors.initials: A
authors.lastname: Galaup
authors.forename: Mélanie
authors.initials: M
authors.lastname: Durand
authors.forename: Jérémie
authors.initials: J
authors.lastname: Teillon
authors.forename: Josette
authors.initials: J
authors.lastname: Philippe
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: Gavin
authors.initials: G
authors.lastname: Thurston
authors.forename: Stéphane
authors.initials: S
authors.lastname: Germain
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002199:Capillary Permeability / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000139:chemically induced / Q000196:embryology / Q000235:genetics / Q000473:pathology; D007365:Intercellular Junctions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009389:Neovascularization, Pathologic / Q000196:embryology* / Q000235:genetics / Q000473:pathology; D010100:Oxygen / Q000633:toxicity; D020286:Pericytes / Q000378:metabolism* / Q000473:pathology; D012160:Retina / Q000196:embryology* / Q000473:pathology; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000196:embryology* / Q000235:genetics / Q000473:pathology
chemical_list: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D010100:Oxygen