HYPOXIC REGULATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN RETINAL CELLS
HYPOXIC REGULATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN RETINAL CELLS
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DOI：
10.1001/archopht.1995.01100120068012
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发表时间：
1995-12-01
影响因子：
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通讯作者：
IWAMOTO, MA
中科院分区：
文献类型：
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作者：
AIELLO, LP;NORTHRUP, JM;IWAMOTO, MA
背景资料：血管内皮生长因子（Vascular endothelial growth factor，VEGF）是一种血管生成蛋白和血管通透性因子，其眼内浓度与糖尿病、视网膜中央静脉阻塞、早产儿视网膜病变和虹膜红变患者的活跃新生血管密切相关。将视网膜色素上皮细胞、周细胞和微血管内皮细胞暴露于体外缺氧条件下，并通过北方印迹分析评估VEGF的RNA表达。通过视网膜内皮细胞生长测定和VEGF中和VEGF受体IgG嵌合蛋白测量培养基的VEGF特异性增殖潜力。VEGFRNA水平在缺氧4小时内升高，18小时后升高3倍至30倍在所有细胞类型中（0%至5%氧气，5%二氧化碳，90%至95%氮气）（0.01 < P <0.03）。刺激依赖于氧浓度。VEGF RNA水平通过恢复常氧24小时而正常化（P <0.004）。缺氧视网膜周细胞和视网膜色素上皮细胞条件培养液刺激视网膜内皮细胞生长20%（P = .04），并且这种刺激被VEGF中和受体嵌合蛋白完全抑制结论：缺氧增加视网膜细胞中VEGF的表达，其促进视网膜内皮细胞增殖，提示VEGF在介导缺血性视网膜疾病引起的眼内新生血管形成中起主要作用。
Background: Vascular endothelial growth factor (VEGF) is an angiogenic protein and vasopermeability factor whose intraocular concentrations are closely correlated with active neovascularization in patients with diabetes mellitus, central retinal vein occlusion, retinopathy of prematurity, and rubeosis iridis.Objective: To determine whether hypoxia could induce expression of VEGF in retinal cells, which then promotes retinal endothelial cell proliferation.Methods: Retinal pigment epithelial cells, pericytes, and microvascular endothelial cells were exposed to hypoxic conditions in vitro, and RNA expression of VEGF was evaluated by Northern blot analysis. The VEGF-specific proliferative potential of the medium was measured by means of retinal endothelial cell growth assays and VEGF-neutralizing VEGF receptor IgG chimeric protein.Results: The VEGF RNA levels increased within 4 hours and reached elevations of threefold to 30-fold after 18 hours of hypoxia (0% to 5% oxygen, 5% carbon dioxide, 90% to 95% nitrogen) in all cell types (.01 < P < .03). Stimulation was dependent on oxygen concentration. The VEGF RNA levels were normalized by reinstitution of normoxia for 24 hours (P < .004). Medium conditioned by hypoxic retinal pericytes and retinal pigment epithelial cells stimulated retinal endothelial cell growth by 20% (P = .04), and this stimulation was entirely inhibited by VEGF-neutralizing receptor chimeric protein (P = .02).Conclusion: Hypoxia increases VEGF expression in retinal cells, which promotes retinal endothelial cell proliferation, suggesting that VEGF plays a major role in mediating intraocular neovascularization resulting from ischemic retinal diseases.