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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.

SUBMITTER: Perdiguero EG 

PROVIDER: S-EPMC3196087 | biostudies-other | 2011 Oct

REPOSITORIES: biostudies-other

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Alteration of developmental and pathological retinal angiogenesis in angptl4-deficient mice.

Perdiguero Elisa Gomez EG   Galaup Ariane A   Durand Mélanie M   Teillon Jérémie J   Philippe Josette J   Valenzuela David M DM   Murphy Andrew J AJ   Yancopoulos George D GD   Thurston Gavin G   Germain Stéphane S  

The Journal of biological chemistry 20110805 42


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  ...[more]

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