Clark D E, Smith S K, He Y, Day K A, Licence D R, Corps A N, Lammoglia R, Charnock-Jones D S
a Reproductive Molecular Research Group, Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, CB2 2SW, United Kingdom.
Biol Reprod. 1998 Dec;59(6):1540-8. doi: 10.1095/biolreprod59.6.1540.
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.
血管内皮生长因子（VEGF）是一种强有力的分泌因子，可促进血管生成并维持内皮的完整性。许多肿瘤中VEGF水平升高，先兆子痫（一种严重的妊娠疾病）女性体内的VEGF水平也会升高。在此我们通过原位杂交表明，滋养层含有编码可溶性VEGF受体Flt-1（sFlt-1：最初由肯德尔和托马斯描述，《美国国家科学院院刊》90：10705 - 10709）的mRNA。对绒毛条件培养基的结合试验和蛋白质印迹证实了sFlt-1的产生。发现孕妇血清中含有一种男性或未怀孕女性血清中不存在的VEGF结合蛋白。通过肝素亲和力、柱分级分离和交联测定，该蛋白与sFlt-1相同。综上所述，这些结果表明胎盘分泌sFlt-1，预期其为一种VEGF拮抗剂。这是体内产生sFlt-1受体的首次报道，揭示了一种自然调节这种强效血管生成因子的新机制。这种拮抗剂的存在表明VEGF作用的调节对于成功妊娠至关重要。这对于VEGF在其他情况下的局部和全身活性具有重要意义。
