内皮素-1可促进子痫前期胎盘静脉收缩：ETAR/ETBR/CaV1.2/CALD1的作用。

IF 3 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta Pub Date : 2024-10-24 DOI:10.1016/j.placenta.2024.10.011

Hongyu Su , Min Li , Na Li , Yingying Zhang , Yun He , Ze Zhang , Yumeng Zhang , Qinqin Gao , Zhice Xu , Jiaqi Tang

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引用次数: 0

摘要

背景：胎盘在子痫前期中起着至关重要的作用。本研究探讨了内皮素-1（ET-1）及其受体在子痫前期胎盘中的作用：方法：从正常妊娠和子痫前期妊娠的一个胎儿中采集胎盘样本。用DMT测量胎盘绒毛膜板血管张力，使用血管活性剂或不使用拮抗剂。使用全细胞膜片钳检测单个平滑肌细胞中 L 型电压依赖性钙通道（CaV1.2）的作用。使用 PCR、Western 印迹和 ELISA 检测分子表达。将胎盘血管外植体和人脐静脉平滑肌细胞（HUVSMC）暴露于含有或不含拮抗剂的 ET-1 处理中。将人脐静脉内皮细胞（HUVEC）和怀孕绵羊置于缺氧条件下，模拟子痫前期：结果：ET-1和IRL1620在子痫前期胎盘静脉中介导了更强的收缩，尽管ETAR表达不变，ETBR表达减少。与对照组相比，子痫前期脐血、母体血浆和胎盘血管中的ET-1含量更高。宫内缺氧会增加胎羔和母羊血浆中的 ET-1。缺氧促进了 HUVEC 中 ET-1 的产生。子痫前期胎盘血管中CaV1.2的作用和表达减少，而平滑肌细胞收缩表型的标志物高分子量钙粘蛋白（CALD1）显著增加。ET-1通过ETAR/ETBR增加了胎盘外植体和HUVSMC中的CALD1：本研究首次证明了ET-1通过ETAR/ETBR而不是通过较弱的CaV1.2诱导子痫前期胎盘绒毛膜板静脉产生更大的收缩。宫内缺氧会促进胎儿羔羊和母羊血浆中的 ET-1，这与子痫前期的情况相似。ET-1与ETAR/ETBR结合会增加CALD1，而CALD1与子痫前期更强的收缩有关。这些数据为子痫前期的发病提供了重要信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Endothelin-1 potentiated constriction in preeclampsia placental veins: Role of ETAR/ETBR/CaV1.2/CALD1

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Endothelin-1 potentiated constriction in preeclampsia placental veins: Role of ETAR/ETBR/CaV1.2/CALD1

Background

Placenta plays a vital role in preeclampsia. The present study investigated the role of endothelin-1 (ET-1) and its receptors in preeclampsia placenta.

Method

Placenta samples were collected from normal and preeclampsia pregnancies, with one single fetus. Placental chorionic plate vessel tone was measured with DMT using vasoactive agents with or without antagonists. Role of L-type voltage-dependent calcium channels (CaV1.2) in single smooth muscle cell was detected using whole-cell patch clamp. PCR, Western blot, and ELISA was used to detect molecule expressions. Placental vessel explants and human umbilical vein smooth muscle cell (HUVSMC) were exposed to ET-1 treatment with or without antagonists. Human umbilical vein endothelial cell (HUVEC) and pregnant sheep was exposed to hypoxic condition, simulating preeclampsia.

Results

ET-1 and IRL1620 mediated stronger contractions in preeclampsia placental veins, despite unchanged ETAR and decreased ETBR expression. Comparing with control, there was higher ET-1 in umbilical plasma, maternal plasma, and placental vessels from preeclampsia. In utero hypoxia increased plasma ET-1 in fetal lambs and ewes. Hypoxia promoted ET-1 production in HUVEC. Role and expression of CaV1.2 was decreased in preeclampsia placental vessels, while high-molecular-weight caldesmon (CALD1), the marker of contractile phenotype of smooth muscle cells, was significantly increased. ET-1 treatment increased CALD1 in placental explants and in HUVSMC via ETAR/ETBR.

Conclusion

The present study firstly demonstrated ET-1 induced greater contraction in preeclampsia placental chorionic plate veins via ETAR/ETBR, instead of via weaker CaV1.2. In utero hypoxia promoted plasma ET-1 in fetal lambs and ewe, similar to that in preeclampsia. ET-1, binding with ETAR/ETBR increased CALD1, which was associated with stronger contraction in preeclampsia. The data provided important information in preeclampsia onset.

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来源期刊

Placenta 医学-发育生物学

CiteScore

6.30

自引率

10.50%

发文量

391

审稿时长

78 days

期刊介绍： Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.