Complex expression changes of the placental endothelin system in early and late onset preeclampsia, fetal growth restriction and gestational diabetes

Complex expression changes of the placental endothelin system in early and late onset preeclampsia, fetal growth restriction and gestational diabetes
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DOI:
10.1016/j.lfs.2012.04.040
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发表时间:
2012-10-15
期刊:
影响因子:
6.1
通讯作者:
Cervar-Zivkovic, Mila
Cervar-Zivkovic, Mila
中科院分区:
医学2区
文献类型:
--
作者:
Dieber-Rotheneder, Martina;Beganovic, Sanja;Cervar-Zivkovic, Mila

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目的:先兆子痫(PE)、胎儿生长受限(FGR)和妊娠期糖尿病(GDM)是影响母胎健康的主要妊娠并发症。胎盘和血管收缩剂内皮素-1 (ET-1)在这些情况下起着控制和调节作用。本研究验证了ET-1及其受体(ETA和ETB)的表达在这些病理中发生改变,并且在妊娠早期(孕周[GW] 34)妊娠晚期之间存在差异的假设。主要方法:研究纳入88例PE(血压140/90 mmHg,蛋白> 300 mg/24小时,n = 14), FGR(< 10出生体重百分位数,病理脐血流量,n = 13), PE + FGR (n = 5)和GDM (n = 21)的女性(GW 28-41),以及孕龄匹配的对照组(n = 35)。采用实时荧光定量PCR和免疫印迹法对胎盘组织中ET-1、ETA和ETB mRNA及ETA和ETB蛋白进行定量分析。主要发现:PE、PE + FGR和GDM中ET/ETR mRNA系统发生改变。ET-1、ETA和ETB在早发性PE和PE + FGR中表达上调,且在PE + FGR中作用更强。妊娠晚期GDM可下调胎盘ET/ETR mRNA表达。ET/ETR蛋白几乎没有变化。意义:早发性PE (
Aims: Preeclampsia (PE), fetal growth restriction (FGR) and gestational diabetes mellitus (GDM) are major pregnancy complications affecting maternal and fetal health. The placenta and the vasoconstrictor endothelin-1 (ET-1) have a controlling and mediating role in these conditions. This study tested the hypothesis that the expression of ET-1 and its receptors (ETA and ETB) is altered in these pathologies and differs between early (gestational week [GW] 34) third trimester pregnancies.Main methods: The study included 88 women (GW 28-41) with PE (blood pressure > 140/90 mmHg, protein > 300 mg/24 hrs; n = 14), FGR (< 10th birthweight centile and pathological umbilical blood flow; n = 13), PE + FGR (n = 5) and GDM (n = 21), and gestational age-matched controls (n = 35). ET-1, ETA and ETB mRNA and ETA and ETB protein were quantified in placental tissues by real-time PCR and immunoblotting.Key findings: The ET/ETR mRNA system is altered in PE and PE + FGR and GDM. Expression of ET-1, ETA and ETB is upregulated in early onset PE and PE + FGR with stronger effect in PE + FGR. GDM down regulated ET/ETR mRNA in the placentas in late third trimester of pregnancy. ET/ETR protein is virtually unchanged.Significance: Early onset PE (