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胎盘来源的细胞外囊泡与子痫前期及相关高凝状态的关联:一项临床观察性研究

Association of placenta-derived extracellular vesicles with pre-eclampsia and associated hypercoagulability: a clinical observational study.

作者信息

Chen Y, Huang P, Han C, Li J, Liu L, Zhao Z, Gao Y, Qin Y, Xu Q, Yan Y, Wang Y, Ren J, Men J, Dong J, Zhang J, Xue F

机构信息

Department of Obstetrics and Gynaecology, Tianjin Medical University General Hospital and Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin, China.

Department of Neurosurgery, Tianjin Medical University General Hospital and Tianjin Neurological Institute, Tianjin, China.

出版信息

BJOG. 2021 May;128(6):1037-1046. doi: 10.1111/1471-0528.16552. Epub 2020 Nov 3.

DOI:10.1111/1471-0528.16552
PMID:33010098
Abstract

OBJECTIVE

Pre-eclampsia (PE) is a pregnancy-associated condition initiated by placental factors. We have demonstrated that placental extracellular vesicles (pcEVs) cause hypertension and proteinuria in pregnant and non-pregnant mice.

STUDY DESIGN

An observational study with both case-control and longitudinal designs.

SETTING

A single centre at the Department of Obstetrics and Gynaecology, Tianjin Medical University.

POPULATION

We collected blood samples and clinical information from 54 PE patients, 33 normally pregnant women at 30-36 gestational weeks and on postpartum days 1 and 4 for the cross-sectional study, and at 22-31, 32-35 and 36-40 weeks for the longitudinal study. Non-pregnant women were also recruited.

METHODS

Blood samples were analysed using flow cytometry, coagulation tests and ELISA.

MAIN OUTCOME MEASURES

The primary outcome was plasma pcEV and other extracellular vesicles (EVs), and their expressions of anionic phospholipids and von Willebrand factor (VWF). Secondary variables included coagulation, ADAMTS-13 and the anionic phospholipid-binding proteins.

RESULTS

Plasma pcEVs progressively increased from pregnant women during non-menstrual period (NW) to PE patients (interquartile range [IQR] for NW: 206/microlitre [116-255], normal pregnancy [NP]: 1108/microlitre [789-1969] and PE: 8487/microlitre [4991-16 752]) and predicted PE. EVs from endothelial cells, platelets and erythrocytes accounted for <10% of pcEVs. VWF became hyper-adhesive in PE patients and contributed to the pregnancy-associated hypercoagulability.

CONCLUSION

Placental, platelet- and endothelial cell-derived EVs were significantly elevated in PE patients, but only pcEVs predicted PE. These EVs played a causal role in the pregnancy-induced hypercoagulability.

TWEETABLE ABSTRACT

Placenta-derived extracellular vesicles predict pre-eclampsia and the associated hypercoagulability.

摘要

目的

子痫前期(PE)是一种由胎盘因素引发的妊娠相关病症。我们已证实胎盘细胞外囊泡(pcEVs)可导致妊娠和非妊娠小鼠出现高血压和蛋白尿。

研究设计

一项采用病例对照和纵向设计的观察性研究。

研究地点

天津医科大学妇产科的一个单一中心。

研究对象

我们收集了54例PE患者、33例孕30 - 36周的正常孕妇以及产后第1天和第4天的血液样本和临床信息用于横断面研究,并在孕22 - 31周、32 - 35周和36 - 40周进行纵向研究。还招募了非妊娠女性。

方法

使用流式细胞术、凝血试验和酶联免疫吸附测定法对血液样本进行分析。

主要观察指标

主要结局是血浆pcEV和其他细胞外囊泡(EVs),以及它们的阴离子磷脂和血管性血友病因子(VWF)的表达。次要变量包括凝血、ADAMTS - 13和阴离子磷脂结合蛋白。

结果

血浆pcEVs从非月经期(NW)的孕妇到PE患者逐渐增加(NW的四分位间距[IQR]:206/微升[116 - 255],正常妊娠[NP]:1108/微升[789 - 1969],PE:8487/微升[4991 - 16752]),并可预测PE。来自内皮细胞、血小板和红细胞的EVs占pcEVs的比例小于10%。VWF在PE患者中变得高黏附,并导致妊娠相关的高凝状态。

结论

PE患者中胎盘、血小板和内皮细胞来源的EVs显著升高,但只有pcEVs可预测PE。这些EVs在妊娠诱导的高凝状态中起因果作用。

可发推文摘要

胎盘来源的细胞外囊泡可预测子痫前期及相关的高凝状态。

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