妊娠期高血压、子痫前期和胎儿生长受限会导致孕妇外周血中与心血管和脑血管疾病相关的微小RNA失调。

Gestational hypertension, preeclampsia and intrauterine growth restriction induce dysregulation of cardiovascular and cerebrovascular disease associated microRNAs in maternal whole peripheral blood.

作者信息

Hromadnikova Ilona, Kotlabova Katerina, Hympanova Lucie, Krofta Ladislav

机构信息

Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.

Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic; Institute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech Republic.

出版信息

Thromb Res. 2016 Jan;137:126-140. doi: 10.1016/j.thromres.2015.11.032. Epub 2015 Nov 22.

DOI:10.1016/j.thromres.2015.11.032

PMID:26632513

Abstract

AIMS

To demonstrate that pregnancy-related complications are associated with alterations in cardiovascular and cerebrovascular microRNA expression. Gene expression of 29 microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p) was assessed in maternal whole peripheral blood, compared between groups (39 gestational hypertension, 68 preeclampsia, 33 intrauterine growth restriction and 20 normal pregnancies) and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. Initially, selection and validation of endogenous controls for microRNA expression studies in patients affected by pregnancy-related complications have been carried out.

RESULTS

The expression profile of microRNAs was different between pregnancy-related complications and controls. The down-regulation of miR-100-5p, miR-125b-5p and miR-199a-5p was a common phenomenon shared between gestational hypertension, preeclampsia, and intrauterine growth restriction. Moreover, IUGR pregnancies induced down-regulation of miR-17-5p, miR-146a-5p, miR-221-3p and miR-574-3p in maternal circulation. Irrespective of the severity of the disease, preeclampsia was associated with the dysregulation of miR-100-5p and miR-125b-5p and IUGR with dysregulation of miR-199a-5p. Preeclampsia requiring termination of gestation before 34 weeks was associated with down-regulation of miR-146a-5p, miR-199a-5p and miR-221-3p. Weak negative correlation between miR-146a-5p and miR-221-3p expression and the pulsatility index in the umbilical artery was found. Additional microRNAs (miR-103a-3p, miR-126-3p, miR-195-5p and miR-499a-5p) showed a trend to down-regulation in appropriate pregnancy-related complications.

CONCLUSION

Epigenetic changes are induced by pregnancy-related complications in maternal whole peripheral blood.

摘要

目的

证明妊娠相关并发症与心血管和脑血管微小RNA表达的改变有关。评估了29种微小RNA（miR-1-3p、miR-16-5p、miR-17-5p、miR-20a-5p、miR-20b-5p、miR-21-5p、miR-23a-3p、miR-24-3p、miR-26a-5p、miR-29a-3p、miR-92a-3p、miR-100-5p、miR-103a-3p、miR-122-5p、miR-125b-5p、miR-126-3p、miR-130b-3p、miR-133a-3p、miR-143-3p、miR-145-5p、miR-146a-5p、miR-181a-5p、miR-195-5p、miR-199a-5p、miR-210-3p、miR-221-3p、miR-342-3p、miR-499a-5p和miR-574-3p）在孕妇外周血中的基因表达，在各组（39例妊娠期高血压、68例先兆子痫、33例胎儿生长受限和20例正常妊娠）之间进行比较，并与疾病严重程度在临床体征、分娩日期和多普勒超声参数方面进行相关性分析。最初，已对受妊娠相关并发症影响患者的微小RNA表达研究的内参进行了选择和验证。

结果

妊娠相关并发症组与对照组之间微小RNA的表达谱不同。miR-100-5p、miR-125b-5p和miR-199a-5p的下调是妊娠期高血压、先兆子痫和胎儿生长受限之间共有的常见现象。此外，胎儿生长受限妊娠导致孕妇循环中miR-17-5p、miR-146a-5p、miR-221-3p和miR-574-3p下调。无论疾病严重程度如何，先兆子痫与miR-100-5p和miR-125b-5p失调相关，胎儿生长受限与miR-199a-5p失调相关。在34周前需要终止妊娠的先兆子痫与miR-146a-5p、miR-199a-5p和miR-221-3p下调相关。发现miR-146a-5p和miR-221-3p表达与脐动脉搏动指数之间存在弱负相关。其他微小RNA（miR-103a-3p、miR-126-3p、miR-195-5p和miR-499a-5p）在适当的妊娠相关并发症中呈下调趋势。