A vascular endothelial growth factor antagonist is produced by the human placenta and released into the maternal circulation
A vascular endothelial growth factor antagonist is produced by the human placenta and released into the maternal circulation
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DOI：
10.1095/biolreprod59.6.1540
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发表时间：
1998-12-01
影响因子：
3.6
通讯作者：
Charnock-Jones, DS
中科院分区：
文献类型：
--
作者：
Clark, DE;Smith, SK;Charnock-Jones, DS
血管内皮生长因子（VEGF）是一种促进血管生成和维持内皮完整性的强效分泌因子。VEGF的水平在许多肿瘤中增加，并且在患有先兆子痫（一种严重的妊娠疾病）的妇女中升高。在此，我们通过原位杂交显示滋养层含有编码称为Flt-1（sFlt-1：最初由Kendall和托马斯描述，PNAS 90：10705-10709）的VEGF受体的可溶形式的mRNA。绒毛条件培养基的结合测定和蛋白质印迹证实了sFlt-1的产生。发现来自孕妇的血清含有VEGF结合蛋白，其不存在于来自男性或非孕妇的血清中。如通过肝素亲和力、柱分级分离和交联所确定的，该蛋白与sFlt-1相同。综上所述，这些结果表明胎盘分泌sFlt-1，预期其为VEGF拮抗剂。这是第一个在体内生产sFlt-1受体的报告，它揭示了一种新的机制，自然调节这种有效的血管生成剂。这种拮抗剂的存在表明，调节VEGF的作用是成功怀孕所必需的。这对VEGF在其他条件下的局部和全身活性具有重要意义。
Vascular endothelial growth factor (VEGF) is a potent secreted factor that promotes angiogenesis and maintains the integrity of the endothelium. Levels of VEGF are increased in many tumors and are elevated in women with pre-eclampsia, a serious disease of pregnancy. Here we show by in situ hybridization that the trophoblast contains the mRNA encoding a soluble version of the VEGF receptor known as Flt-1 (sFlt-1: initially described by Kendall and Thomas, PNAS 90:10705-10709), Binding assays and Western blotting of villus-conditioned media confirmed the production of sFlt-1, Serum from pregnant women was found to contain a VEGF-binding protein that was not present in serum from men or nonpregnant women. As determined by heparin affinity, column fractionation, and cross-linking, this protein was identical to sFlt-1. Taken together, these results show that the placenta secretes sFlt-1, which would be expected to be a VEGF antagonist. This is the first report of production of the sFlt-1 receptor in vivo, and it reveals a new mechanism for naturally regulating this potent angiogenic agent. The presence of such an antagonist suggests that regulation of VEGF action is essential to successful pregnancy. This has important implications for the activity of VEGF locally and systemically in other conditions.