Alteration of Developmental and Pathological Retinal Angiogenesis in angptl4-deficient Mice
Alteration of Developmental and Pathological Retinal Angiogenesis in angptl4-deficient Mice
复制标题
DOI：
10.1074/jbc.m111.220061
复制
发表时间：
2011-10-21
影响因子：
4.8
通讯作者：
Germain, Stephane
中科院分区：
文献类型：
--
作者：
Perdiguero, Elisa Gomez;Galaup, Ariane;Germain, Stephane
适当的血管成熟、内皮连接的重塑和血管周围细胞的募集对于建立和维持血管功能至关重要。在增殖性视网膜病变中，缺氧诱导的血管生成与血管屏障破坏、水肿和视力丧失有关。因此，确定调节血管成熟的因素对靶向病理性血管生成至关重要。鉴于目前文献报道的血管生成素样4 （ANGPTL4）在体外和体内功能系统增益中的相互矛盾的作用，本研究的目的是表征血管生成，重点关注angpl4缺陷小鼠的围产期视网膜血管化和病理情况。我们报告了内皮连接和周细胞覆盖改变的组织，两者都导致血管生成受损和最终被捕获的血管泄漏增加，表明血管成熟延迟。在氧诱导视网膜病变模型中，angptl4缺陷小鼠的组织缺氧引起的病理性新生血管也被强烈抑制。因此，这项研究表明，在发育和病理状态下，ANGPTL4调节内皮细胞连接组织和周细胞覆盖，控制血管通透性和血管生成。
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.