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通过检测血管生成蛋白和体外血管生成/血管发生试验评估子痫前期和非复杂性妊娠的血管生成能力。

Angiogenic capacity in pre-eclampsia and uncomplicated pregnancy estimated by assay of angiogenic proteins and an in vitro vasculogenesis/angiogenesis test.

机构信息

Department of Obstetrics and Gynaecology, Tampere University Central Hospital, Tampere, Finland.

FICAM, Finnish Centre for Alternative Methods, School of Medicine, University of Tampere, Tampere, Finland.

出版信息

Angiogenesis. 2019 Feb;22(1):67-74. doi: 10.1007/s10456-018-9637-2. Epub 2018 Jul 12.

Abstract

OBJECTIVE

The purpose of the study was to determine the angiogenic capacity of sera in early and late pregnancy and in umbilical blood serum after childbirth, and to define how angiogenic properties assessed in a functional in vitro test are related to individual angiogenic proteins in six women with pre-eclampsia and in six healthy pregnant controls.

METHODS

Maternal first and third trimester serum samples, and umbilical blood samples after childbirth, were tested in an in vitro human adipose stromal cell-human umbilical vein endothelial cell (hASC-HUVEC) vasculogenesis/angiogenesis assay. The angiogenic properties of the samples were measured by quantifying tubule formation. Concentrations of total placental growth factor (PlGF), total vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) were determined by immunoassay.

RESULTS

First-trimester maternal sera of both groups had a stimulatory effect on angiogenesis in vitro and levels of angiogenic proteins did not differ between the groups. Third-trimester maternal sera in the pre-eclampsia group had an inhibitory effect on tubule formation, while those from normal pregnancies remained stimulatory. Compared with the first trimester there was a significant change in the concentrations of angiogenic proteins toward an anti-angiogenic state in pre-eclampsia. Umbilical blood serum exhibited strong anti-angiogenic effects without a significant difference between groups.

CONCLUSIONS

Third-trimester serum of pre-eclamptic patients is anti-angiogenic. This phenomenon is not yet present in the first trimester. Umbilical blood serum shows inhibitory effects on angiogenesis after normal as well as pre-eclamptic pregnancy.

摘要

目的

本研究旨在确定早孕期、晚孕期及产后脐血血清的血管生成能力,并探讨功能体外试验中评估的血管生成特性与 6 例早发性子痫前期和 6 例健康孕妇对照个体血管生成蛋白之间的关系。

方法

在体外人脂肪基质细胞-人脐静脉内皮细胞(hASC-HUVEC)血管生成/血管形成试验中检测母体第一和第三孕期血清样本和产后脐血样本。通过定量管腔形成来测量样本的血管生成特性。通过免疫测定法测定总胎盘生长因子(PlGF)、总血管内皮生长因子(VEGF)、可溶性 fms 样酪氨酸激酶 1(sFlt-1)和可溶性内皮糖蛋白(sEng)的浓度。

结果

两组的第一孕期母体血清均对体外血管生成具有刺激作用,且两组之间血管生成蛋白的水平无差异。早发性子痫前期组的第三孕期母体血清对管腔形成具有抑制作用,而正常妊娠组的母体血清仍具有刺激作用。与第一孕期相比,早发性子痫前期组中血管生成蛋白的浓度发生了显著变化,向抗血管生成状态转变。脐血血清表现出强烈的抗血管生成作用,但两组之间无显著差异。

结论

早发性子痫前期患者的第三孕期血清具有抗血管生成作用。这种现象在第一孕期尚未出现。正常妊娠和早发性子痫前期后,脐血血清对血管生成均具有抑制作用。

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