Recombinant human VEGF165b inhibits experimental choroidal neovascularization.
Recombinant human VEGF165b inhibits experimental choroidal neovascularization.
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DOI：
10.1167/iovs.09-4360
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发表时间：
2010-08
影响因子：
4.4
通讯作者：
Hinton DR
中科院分区：
文献类型：
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作者：
Hua J;Spee C;Kase S;Rennel ES;Magnussen AL;Qiu Y;Varey A;Dhayade S;Churchill AJ;Harper SJ;Bates DO;Hinton DR
血管内皮生长因子（VEGF-A）是湿性年龄相关性黄斑变性（AMD）血管生成的主要刺激因子。然而，VEGF-A通过选择性剪接产生为两个家族，促血管生成VEGF-Axxx家族和抗血管生成VEGF-Axxxb家族。它是促血管生成家族，负责在AMD中看到的血管生长。为了确定VEGF-A的抗血管生成同种型作为脉络膜新生血管形成抑制剂的作用，我们采用了小鼠眼中激光诱导的脉络膜新生血管形成模型，并研究了VEGF-A165 b对体外内皮细胞和VEGFR的作用。VEGF-A165 b抑制VEGF-A165介导的内皮细胞迁移的剂量效应与雷珠单抗和贝伐单抗相似，比哌加他尼强200倍。VEGF-A165 b以与VEGF-A165相似的亲和力结合VEGFR 1和VEGFR 2。激光损伤后，小鼠眼内或皮下注射重组人VEGF-A165 b。眼内注射rhVEGF-A165 b对荧光素渗漏产生明显的剂量依赖性抑制，IC 50为16 pg/眼，新生血管形成（IC 50 0.8 pg/眼）和损伤通过组织学染色评估（IC 50 8 pg/眼）。每周两次皮下给药100μg也可抑制荧光素渗漏和新生血管形成，并缩小病变大小。这些结果表明，VEGF-A165 b在年龄相关性黄斑变性的小鼠模型中是有效的抗血管生成剂，并表明增加抗血管生成亚型与促血管生成亚型的比率在这种情况下可能是治疗有效的。
Vascular Endothelial growth Factor (VEGF-A) is the principal stimulator of angiogenesis in wet age related macular degeneration (AMD). However, VEGF-A is generated by alternate splicing into two families, the pro-angiogenic VEGF-Axxx family, and the anti-angiogenic VEGF-Axxxb family. It is the pro-angiogenic family that is responsible for the blood vessel growth seen in AMD. To determine the role of anti-angiogenic isoforms of VEGF-A as inhibitors of choroidal neovascularisation we employed a model of laser induced choroidal neovascularisation in the mouse eye, and investigated VEGF-A165b effects on endothelial cells and VEGFRs in vitro. VEGF-A165b inhibited VEGF-A165-mediated endothelial cell migration with a similar dose effect as ranibizumab and bevacizumab, and 200 fold more potently than pegaptanib. VEGF-A165b bound both VEGFR1 and VEGFR2 with similar affinity to VEGF-A165. After laser injury mice were injected either intraocularly or subcutaneously with recombinant human VEGF-A165b. Intraocular injection of rhVEGF-A165b gave a pronounced dose dependent inhibition of fluorescein leakage, with an IC50 of 16pg/eye, neovascularisation (IC50 0.8pg/eye) and lesion as assessed by histological staining (IC50 8pg/eye). Subcutaneous administration of 100μg twice a week also inhibited fluorescein leakage and neovascularisation and reduced lesion size. These results show that VEGF-A165b is a potent anti-angiogenic agent in mouse model of age related macular degeneration, and suggest that increasing the ratio of anti-to-pro-angiogenic isoforms may be therapeutically effective in this condition.
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影响因子：
4.4
作者：
Gaudreault, J;Fei, D;Shiu, V
通讯作者：
Shiu, V
影响因子：
158.5
作者：
Eremina, Vera;Jefferson, J. Ashley;Quaggin, Susan E.
通讯作者：
Quaggin, Susan E.
影响因子：
158.5
作者：
Brown, David M.;Kaiser, Peter K.;Schneider, Susan
通讯作者：
Schneider, Susan
影响因子：
50.3
作者：
Casanovas, O;Hicklin, DJ;Hanahan, D
通讯作者：
Hanahan, D
DOI：
10.1038/nrc2442
发表时间：
2008-08
期刊：
Nature reviews. Cancer
影响因子：
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作者：
通讯作者：
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