Promoter methylation changes and vascular dysfunction in pre-eclamptic umbilical vein

Qinqin Gao,Huan Li,Hongmei Ding,Jianying Tao,Xiaorong Fan,Zhice Xu,Yuxian Yang,Yun He,Ting Xu,Jie Chen

doi:10.1186/s13148-019-0685-2

Abstract

BackgroundHypertension is one of primary clinical presentations of pre-eclampsia. The occurrence and progress of hypertension are closely related to vascular dysfunction. However, information is limited regarding the pathological changes of vascular functions in pre-eclamptic fetuses. Human umbilical cord vein was used to investigate the influence of pre-eclampsia on fetal blood vessels in this study.ResultsThe present study found that the vasoconstriction responses to arginine vasopressin (AVP) and oxytocin (OXT) were attenuated in the pre-eclamptic umbilical vein as compared to in normal pregnancy, which was related to the downregulated AVP receptor 1a (AVPR1a), OXT receptor (OXTR), and protein kinase C isoform β (PKCβ), owing to the deactivated gene transcription, respectively. The deactivated AVPR1a, OXTR, and PKCB gene transcription were respectively linked with an increased DNA methylation within the gene promoter.ConclusionsTo the best of our knowledge, this study first revealed that a hyper-methylation in gene promoter, leading to relatively reduced patterns of AVPR1a, OXTR, and PKCB expressions, which was responsible for the decreased sensitivity to AVP and OXT in the umbilical vein under conditions of pre-eclampsia. The data offered new and important information for further understanding the pathological features caused by pre-eclampsia in the fetal vascular system, as well as roles of epigenetic-mediated gene expression in umbilical vascular dysfunction.

Highlights

Hypertension is one of primary clinical presentations of pre-eclampsia
There were no significant differences in Potassium chloride (KCl)-induced maximal contraction between Normal pregnancies (NP) and PE group (Fig. 1b, e), whereas, the Emax (AVP- or OXT-induced contraction at 10−4 mol/L) and pD2 (−log[50% effective concentration]) values for arginine vasopressin (AVP) and OXT were significantly decreased in pre-eclamptic umbilical vein (Fig. 1c, f )
These data indicated that pre-eclamptic umbilical vein was significantly insensitive to AVP and OXT

Summary

Introduction

Hypertension is one of primary clinical presentations of pre-eclampsia. The occurrence and progress of hypertension are closely related to vascular dysfunction. Human umbilical cord vein was used to investigate the influence of pre-eclampsia on fetal blood vessels in this study. Pre-eclampsia (PE) is a leading cause of maternal morbidity, mortality, and premature birth in both developed and developing countries [1, 2]. PE in women is a multi-systemic syndrome with unknown etiology, hypertension is a primary clinical presentation of PE. As a surrogate end point for vascular risk, vascular dysfunction is closely related to the occurrence and progress of hypertension. The umbilical cord is a conduit between the developing fetus and placenta. Umbilical cord vessels are primary vascular structures that may reflect problems

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Conclusion