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循环中组织金属蛋白酶抑制剂 3 的水平升高,该蛋白对血管生成具有抑制作用,在子痫前期中增加。

Circulating levels of tissue inhibitor of metalloproteinase 3, a protein with inhibitory effects on angiogenesis, are increased in pre-eclampsia.

机构信息

Department of Surgery, School of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.

Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA.

出版信息

Int J Gynaecol Obstet. 2023 May;161(2):544-551. doi: 10.1002/ijgo.14552. Epub 2022 Nov 21.

DOI:10.1002/ijgo.14552
PMID:36333976
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10171830/
Abstract

OBJECTIVE

To assess and compare circulating tissue inhibitor of metalloproteinase 3 (TIMP-3) concentrations between women with pre-eclampsia and healthy pregnant women. We also aimed to determine the relationships between circulating TIMP-3 and matrix metalloproteinase 2 (MMP-2), MMP-9, TIMP-1, and TIMP-2 concentrations in pre-eclampsia.

METHODS

A primary case-control study included patients with pre-eclampsia (n = 219) and gestational hypertension (n = 118), healthy pregnant women (n = 214), and non-pregnant women (n = 66), and a replication case-control study included patients with pre-eclampsia (n = 177) and healthy pregnant women (n = 124), all from southeastern Brazil. Plasma TIMP-3, MMP-2, MMP-9, TIMP-1, and TIMP-2 concentrations were assessed using commercially available enzyme-linked immunosorbent assay kits, and the relationships between them were analyzed using Spearman's correlation.

RESULTS

In our primary study, patients with pre-eclampsia and gestational hypertension exhibited increased TIMP-3 concentrations compared with healthy pregnant women (both P < 0.0001) and non-pregnant women (both P < 0.001). These findings were confirmed in the replication study, showing elevated TIMP-3 concentrations in women with pre-eclampsia versus healthy pregnant women (P < 0.001). We found no difference in TIMP-3 concentrations between early-onset and late-onset pre-eclampsia. Moreover, TIMP-3 concentrations were significantly correlated with plasma concentrations of TIMP-1 (r = 0.2333; P = 0.0086) and MMP-2 (r = 0.2159; P = 0.0156) in pre-eclampsia.

CONCLUSIONS

Circulating TIMP-3 concentration is increased in women with pre-eclampsia compared with healthy pregnant women, and it is positively correlated with plasma MMP-2 and TIMP-1 concentrations in pre-eclampsia.

摘要

目的

评估和比较先兆子痫患者与健康孕妇的循环组织金属蛋白酶抑制剂 3(TIMP-3)浓度。我们还旨在确定先兆子痫患者中循环 TIMP-3 与基质金属蛋白酶 2(MMP-2)、MMP-9、TIMP-1 和 TIMP-2 浓度之间的关系。

方法

一项初步的病例对照研究纳入了来自巴西东南部的先兆子痫患者(n=219)、妊娠期高血压患者(n=118)、健康孕妇(n=214)和非孕妇(n=66),一项复制病例对照研究纳入了先兆子痫患者(n=177)和健康孕妇(n=124)。使用商业可得的酶联免疫吸附测定试剂盒评估血浆 TIMP-3、MMP-2、MMP-9、TIMP-1 和 TIMP-2 浓度,并使用 Spearman 相关分析分析它们之间的关系。

结果

在我们的初步研究中,与健康孕妇(均 P<0.0001)和非孕妇(均 P<0.001)相比,先兆子痫和妊娠期高血压患者的 TIMP-3 浓度升高。在复制研究中也得到了同样的结果,与健康孕妇相比,先兆子痫患者的 TIMP-3 浓度升高(P<0.001)。我们没有发现早发型和晚发型先兆子痫患者之间 TIMP-3 浓度的差异。此外,在先兆子痫患者中,TIMP-3 浓度与血浆 TIMP-1 浓度(r=0.2333;P=0.0086)和 MMP-2 浓度(r=0.2159;P=0.0156)呈显著正相关。

结论

与健康孕妇相比,先兆子痫患者的循环 TIMP-3 浓度升高,并且与先兆子痫患者的血浆 MMP-2 和 TIMP-1 浓度呈正相关。

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