Apelin Is a Crucial Factor for Hypoxia-Induced Retinal Angiogenesis
Apelin Is a Crucial Factor for Hypoxia-Induced Retinal Angiogenesis
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DOI：
10.1161/atvbaha.110.209775
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发表时间：
2010-11-01
影响因子：
8.7
通讯作者：
Maeda, Sadaaki
中科院分区：
文献类型：
--
作者：
Kasai, Atsushi;Ishimaru, Yuki;Maeda, Sadaaki
方法和结果缺血性视网膜疾病如糖尿病视网膜病变的进展与病理性视网膜血管生成密切相关，主要由血管内皮生长因子（VEGF）和促红细胞生成素诱导。虽然使用抗VEGF药物的抗血管生成疗法在治疗视网膜新生血管中是有效的，但它们显示出短暂的功效并引起一般不良反应。需要新的治疗靶分子来解决这些问题。最近的研究表明，apelin/APJ系统，一个新的去乙酰化的G蛋白偶联受体系统，参与生理性视网膜血管化。在氧诱导的视网膜病变的小鼠模型中，在缺氧诱导的视网膜血管生成期间检查视网膜血管造影和mRNA表达。与年龄匹配的对照小鼠相比，在氧诱导的视网膜病变模型小鼠中，视网膜apelin表达在缺氧阶段显著增加。APJ共定位于增殖细胞中，这些增殖细胞可能是玻璃体中异位血管的内皮细胞。尽管在氧诱导的视网膜病变模型小鼠中VEGF和促红细胞生成素mRNA上调，但Apelin缺乏几乎不诱导缺氧诱导的视网膜血管生成。爱帕琳小干扰RNA抑制内皮细胞的增殖独立的VEGF/VEGF受体2 signalingpathway. Conclusion-这些结果表明，爱帕琳是缺氧诱导的视网膜血管生成的先决条件。（Arterioscler Thromb Vasc Biol.2010; 30：2182-2187.）
Objective-To investigate the role of endogenous apelin in pathological retinal angiogenesis.Methods and Results-The progression of ischemic retinal diseases, such as diabetic retinopathy, is closely associated with pathological retinal angiogenesis, mainly induced by vascular endothelial growth factor (VEGF) and erythropoietin. Although antiangiogenic therapies using anti-VEGF drugs are effective in treating retinal neovascularization, they show a transient efficacy and cause general adverse effects. New therapeutic target molecules are needed to resolve these issues. It was recently demonstrated that the apelin/APJ system, a newly deorphanized G protein-coupled receptor system, is involved in physiological retinal vascularization. Retinal angiography and mRNA expression were examined during hypoxia-induced retinal angiogenesis in a mouse model of oxygen-induced retinopathy. Compared with age-matched control mice, retinal apelin expression was dramatically increased during the hypoxic phase in oxygen-induced retinopathy model mice. APJ was colocalized in proliferative cells, which were probably endothelial cells of the ectopic vessels in the vitreous body. Apelin deficiency hardly induced hypoxia-induced retinal angiogenesis despite the upregulation of VEGF and erythropoietin mRNA in oxygen-induced retinopathy model mice. Apelin small and interfering RNA suppressed the proliferation of endothelial cells independent of the VEGF/VEGF receptor 2 signaling pathway.Conclusion-These results suggest that apelin is a prerequisite factor for hypoxia-induced retinal angiogenesis. (Arterioscler Thromb Vasc Biol. 2010; 30: 2182-2187.)