VEGFR2 alteration in Alzheimer's disease.
VEGFR2 alteration in Alzheimer's disease.
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DOI：
10.1038/s41598-017-18042-1
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发表时间：
2017-12-18
影响因子：
4.6
通讯作者：
Koh YH
中科院分区：
文献类型：
--
作者：
Cho SJ;Park MH;Han C;Yoon K;Koh YH
阿尔茨海默病(AD)是一种常见的老年人进行性认知功能下降的疾病。血管内皮生长因子(VEGF)等血管生成相关因子可能参与AD的发病过程。可溶性的血管内皮生长因子受体很可能是血管内皮生长因子的内在负性对应物。采用双抗体夹心ELISA法测定了120例正常人、75例轻度认知障碍和76例AD患者血浆中血管内皮生长因子及其两种可溶性受体(sVEGFR1和sVEGFR2)的水平。AD患者血浆中的血管内皮生长因子水平明显高于健康对照组。而AD患者血浆sVEGFR1和sVEGFR2水平明显低于正常对照组。人脐静脉内皮细胞经淀粉样β蛋白处理后，VEGFR2的mRNA水平显著降低。此外，AD模型小鼠大脑中VEGFR2的蛋白水平也降低。此外，我们还发现，转染Notch胞内结构域后，sVEGFR2和VEGFR2的表达也降低。这些结果表明，血管内皮生长因子及其两种受体水平的改变可能与阿尔茨海默病的风险有关。
Alzheimer’s disease (AD) is a common disorder of progressive cognitive decline among elderly subjects. Angiogenesis-related factors including vascular endothelial growth factor (VEGF) might be involved in the pathogenesis of AD. Soluble form of the VEGF receptor is likely to be an intrinsic negative counterpart of VEGF. We measured the plasma levels of VEGF and its two soluble receptors (sVEGFR1 and sVEGFR2) in 120 control subjects, 75 patients with mild cognitive impairment, and 76 patients with AD using ELISA. Plasma levels of VEGF in patients with AD were higher than those in healthy control subjects. However, plasma levels of sVEGFR1 and sVEGFR2 were lower in patients with AD than in healthy control subjects. Levels of VEGFR2 mRNA were significantly decreased in human umbilical vein endothelial cells after amyloid-beta treatment. Further, protein levels of VEGFR2 were also decreased in the brains of AD model mice. In addition, we show that the expression of sVEGFR2 and VEGFR2 was also decreased by the transfection with the Notch intracellular domain. These results indicate that the alterations of VEGF and its two receptors levels might be associated with those at risk for Alzheimer’s disease.
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