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胎盘 sFLT1(可溶性 fms 样酪氨酸激酶受体 1)增加导致子痫前期前母体血清的抗血管生成特征,但不导致胎儿生长受限。

Increased Placental sFLT1 (Soluble fms-Like Tyrosine Kinase Receptor-1) Drives the Antiangiogenic Profile of Maternal Serum Preceding Preeclampsia but Not Fetal Growth Restriction.

机构信息

Department of Obstetrics and Gynaecology (F.G., U.S., S.G., E.C., D.S.C.-J., G.C.S.S.), University of Cambridge, United Kingdom.

Centre for Trophoblast Research (F.G., U.S., D.S.C.-J., G.C.S.S.), University of Cambridge, United Kingdom.

出版信息

Hypertension. 2023 Feb;80(2):325-334. doi: 10.1161/HYPERTENSIONAHA.122.19482. Epub 2022 Jul 22.

Abstract

BACKGROUND

Preeclampsia and fetal growth restriction (FGR) are both associated with an increased ratio of sFLT1 (soluble fms-like tyrosine kinase-1) to PlGF (placenta growth factor) in maternal serum. In preeclampsia, it is assumed that increased placental release of sFLT1 results in PlGF being bound and inactivated. However, direct evidence for this model is incomplete, and it is unclear whether the same applies in FGR.

METHODS

We conducted a prospective cohort study where we followed 4212 women having first pregnancies from their dating ultrasound, obtained blood samples serially through the pregnancy, and performed systematic sampling of the placenta after delivery. The aim of the present study was to determine the relationship between protein levels of sFLT1 and PlGF in maternal serum measured at ≈36 weeks and placental tissue lysates obtained after term delivery in 82 women with preeclampsia, 50 women with FGR, and 132 controls.

RESULTS

The sFLT1:PlGF ratio was increased in both preeclampsia and FGR in both the placenta and maternal serum. However, in preeclampsia, the maternal serum ratio of sFLT1:PlGF was strongly associated with placental sFLT1 level (r=0.45; <0.0001) but not placental PlGF level (r=-0.17; =0.16). In contrast, in FGR, the maternal serum ratio of sFLT1:PlGF was strongly associated with placental PlGF level (r=-0.35; =0.02) but not sFLT1 level (r=0.04; =0.81).

CONCLUSIONS

We conclude that the elevated sFLT1:PlGF ratio is primarily driven by increased placental sFLT1 in preeclampsia, whereas in FGR, it is primarily driven by decreased placental PlGF.

摘要

背景

子痫前期和胎儿生长受限(FGR)均与母体血清中可溶性 fms 样酪氨酸激酶-1(sFLT1)与胎盘生长因子(PlGF)的比值升高有关。在子痫前期中,认为胎盘释放的 sFLT1 增加导致 PlGF 结合并失活。然而,该模型的直接证据并不完整,尚不清楚在 FGR 中是否同样适用。

方法

我们进行了一项前瞻性队列研究,对 4212 名首次妊娠的妇女进行了随访,从其超声检查开始,在整个妊娠过程中连续采集血液样本,并在分娩后进行胎盘系统采样。本研究的目的是确定 82 例子痫前期、50 例 FGR 和 132 例对照组妇女在 ≈36 周时测量的母体血清中 sFLT1 和 PlGF 的蛋白水平与足月分娩后胎盘组织裂解物之间的关系。

结果

子痫前期和 FGR 患者的胎盘和母血清中 sFLT1:PlGF 比值均升高。然而,在子痫前期中,母体血清 sFLT1:PlGF 比值与胎盘 sFLT1 水平密切相关(r=0.45;<0.0001),而与胎盘 PlGF 水平无关(r=-0.17;=0.16)。相比之下,在 FGR 中,母体血清 sFLT1:PlGF 比值与胎盘 PlGF 水平密切相关(r=-0.35;=0.02),而与 sFLT1 水平无关(r=0.04;=0.81)。

结论

我们得出结论,在子痫前期中,升高的 sFLT1:PlGF 比值主要是由胎盘 sFLT1 增加引起的,而在 FGR 中,主要是由胎盘 PlGF 减少引起的。

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