Hyper-methylation of AVPR1A and PKCB gene associated with insensitivity to arginine vasopressin in human pre-eclamptic placental vasculature
Hyper-methylation of AVPR1A and PKCB gene associated with insensitivity to arginine vasopressin in human pre-eclamptic placental vasculature
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AVPR1A 和 PKCα 基因的高甲基化与人先兆子痫胎盘脉管系统对精氨酸加压素不敏感相关
DOI：
10.1016/j.ebiom.2019.05.056
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发表时间：
2019-06-01
期刊：
影响因子：
11.1
通讯作者：
Xu, Zhice
中科院分区：
文献类型：
--
作者：
Gao, Qinqin;Li, Huan;Xu, Zhice
背景：先兆子痫是孕产妇死亡和发病的主要原因。虽然导致先兆子痫的确切机制尚不清楚，但不可否认的是，胎盘功能和循环异常是先兆子痫发生的中心。精氨酸加压素（AVP）作为一种有效的血管收缩剂，长期以来一直参与控制胎盘血管张力和循环;其分泌在先兆子痫循环中显著升高。方法：通过对正常和先兆子痫孕妇胎盘血管进行血管功能和分子水平的检测，探讨先兆子痫患者胎盘血管调节的病理生理学特点及相应的分子机制。本研究发现，胎盘血管对AVP的收缩反应在先兆子痫中比在正常妊娠中减弱。AVP的不敏感性与下调AVP受体1a（AVPR 1A，AVPR 1A基因）和蛋白激酶C亚型β（PKC β，PKC β基因），特别是超甲基化介导的AVPR 1A和PKC β基因下调，分别。解释：研究结果共同揭示，异常DNA甲基化介导的基因表达与血管功能障碍先兆子痫胎盘循环。(C)2019作者由爱思唯尔公司出版
Background: Pre-eclampsia is a leading cause of maternal mortality and morbidity. Although the exact mechanisms that cause pre-eclampsia remain unclear, it is undeniable that abnormal placental function and circulation are a center for initiation pre-eclampsia. As a potent vasoconstrictor, arginine vasopressin (AVP) has long been implicated in controlling placental vascular tone and circulation; its secretion is grossly elevated in pre-eclamptic circulation. However, little is known about the reactivity of AVP in pre-eclamptic placental vasculature.Methods: To reveal the special features of placental vascular regulations with placental pathophysiological changes, as well as the corresponding molecular mechanisms under pre-eclamptic conditions, vascular function and molecular assays were conducted with placental vessel samples from normal and pre-eclamptic pregnancies.Findings: The present study found that vasoconstriction responses of placental vessels to AVP were attenuated in pre-eclampsia as compared to in normal pregnancy. The insensitivity of AVP was correlated with the down-regulated AVP receptor 1a (AVPR1A, AVPR1A gene) and protein kinase C isoform beta (PKC beta, PKC Beta gene), particularly the hyper-methylation-mediated AVPR1A and PKC Beta gene down-regulation, respectively.Interpretation: The findings collectively revealed that aberrant DNA methylation-mediated gene expressions are correlated with vascular dysfunction in pre-eclamptic placental circulation. (C) 2019 The Authors. Published by Elsevier B.V.