Hyper-methylation of AVPR1A and PKCΒ gene associated with insensitivity to arginine vasopressin in human pre-eclamptic placental vasculatureResearch in context

• Main Authors: Qinqin Gao, Huan Li, Hongmei Ding, Xiaorong Fan, Ting Xu, Jiaqi Tang, Yanping Liu, Xueyi Chen, Xiuwen Zhou, Jianying Tao, Zhice Xu
• Format: Article
• Language: English
• Published: Elsevier 2019-06-01
• Series: EBioMedicine
• Online Access: http://www.sciencedirect.com/science/article/pii/S2352396419303640

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 β (PKCβ, PKCΒ gene), particularly the hyper-methylation-mediated AVPR1A and PKCΒ 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. Fund: This work was supported by National Nature & Science Foundation of China. “333 Project”, “Six one project”, “Shuang Chuang Tuan Dui” and Key Discipline “Fetal medicine” of Jiangsu Province, and the Suzhou city “Wei Sheng Ren Cai” program. Subject codes: Vascular biologyPlacental vascular dysfunctionPre-eclampsia. Keywords: Pre-eclampsia, Arginine vasopressin, AVPR1A and PKCβ, DNA methylation, Placental vascular dysfunction