Division of Nephrology and Hypertension (T.L.W.), Mayo Clinic, Rochester, Minnesota 55905; Beth Israel Deaconess Medical Center (A.R.), Boston, Massachusetts 02215; Magee-Womens Research Institute (A.C.M., L.R.E., R.W.P., J.M.R., R.E.G., C.A.H.), and Department of Obstetrics, Gynecology, and Reproductive Sciences (R.W.P., J.M.R., C.A.H.), University of Pittsburgh, Pittsburgh, Pennsylvania 15213; Department of Environmental and Occupational Health (R.E.G., C.A.H.), and Department of Epidemiology (J.M.R.), Graduate School of Public Health (J.M.R.), University of Pittsburgh, Pittsburgh, Pennsylvania 15261; and Clinical and Translational Science Institute (J.M.R.), University of Pittsburgh, Pittsburgh, Pennsylvania 15260.
J Clin Endocrinol Metab. 2014 Mar;99(3):978-87. doi: 10.1210/jc.2013-3277. Epub 2013 Dec 11.
Research examining the source of excess soluble fms-like tyrosine kinase 1 (sFLT1) in preeclampsia has focused on the placenta. The potential contribution of the releasable store of sFLT1 in the systemic vasculature is unknown.
We asked whether the nonplacental releasable store of sFLT1 is larger in women with previous preeclampsia than in women with a previous uncomplicated pregnancy.
We administered heparin to nulligravid women and to women with previous preeclampsia or a previous uncomplicated pregnancy. We compared post-heparin sFLT1 concentrations with those observed in uncomplicated pregnancy and preeclampsia.
The study was performed at Magee-Womens Hospital.
Participants included nulligravidas (n = 8), women 6-24 months postpartum (previous uncomplicated pregnancy, n = 16; previous preeclampsia, n = 15), and pregnant women (uncomplicated pregnancy, n = 30; preeclampsia, n = 25).
Nonpregnant women received an unfractionated heparin bolus.
Pre- and post-heparin plasma sFLT1, placental growth factor, and vascular endothelial growth factor were measured.
In nonpregnant women, heparin increased plasma sFLT1 by 250-fold (P < .01), increased placental growth factor by 7-fold (P < .01), and decreased free vascular endothelial growth factor (P < .01). These changes did not differ between nulligravidas, women with previous preeclampsia, and women with a previous uncomplicated pregnancy. Post-heparin sFLT1 in nonpregnant women was higher than sFLT1 in uncomplicated pregnancy, but lower than sFLT1 in preeclampsia. Baseline and post-heparin sFLT1 were positively correlated (r(2) = 0.19; P < .01). Heparin increased the concentration of the 100-kDa sFLT1 isoform. Adding heparin to whole blood or plasma did not increase sFLT1.
Nonpregnant women have a significant vascular store of releasable sFLT1. The size of this store does not differ between women with previous preeclampsia vs women with previous uncomplicated pregnancy.
研究检查了子痫前期中过量可溶性 fms 样酪氨酸激酶 1（sFLT1）的来源，其重点主要集中在胎盘上。但是，系统血管中 sFLT1 可释放储存库的潜在贡献尚不明确。
我们想知道与既往无并发症妊娠的女性相比，既往有子痫前期的女性非胎盘可释放储存库的 sFLT1 是否更大。
我们给未生育的女性、既往有子痫前期或无并发症妊娠的女性应用肝素。我们将肝素后的 sFLT1 浓度与无并发症妊娠和子痫前期的观察值进行比较。
本研究在 Magee-Womens 医院进行。
参与者包括未生育的女性（n = 8）、产后 6-24 个月的女性（既往无并发症妊娠，n = 16；既往子痫前期，n = 15）和孕妇（无并发症妊娠，n = 30；子痫前期，n = 25）。
未怀孕的女性接受非肠道肝素冲击。
测量肝素前和肝素后的血浆 sFLT1、胎盘生长因子和血管内皮生长因子。
在未怀孕的女性中，肝素将血浆 sFLT1 增加了 250 倍（P <.01），将胎盘生长因子增加了 7 倍（P <.01），并降低了游离血管内皮生长因子（P <.01）。未生育的女性、既往有子痫前期的女性和既往有无并发症妊娠的女性之间这些变化没有差异。非怀孕女性的肝素后 sFLT1 高于无并发症妊娠，低于子痫前期。基线和肝素后 sFLT1 呈正相关（r 2 = 0.19；P <.01）。肝素增加了 100 kDa sFLT1 同工型的浓度。向全血或血浆中添加肝素不会增加 sFLT1。
未怀孕的女性具有重要的可释放 sFLT1 血管储存库。该储存库的大小在既往有子痫前期的女性与既往有无并发症妊娠的女性之间没有差异。
