Hyper-Methylation of <i>AVPR1A</i> and <i>PKCB</i> Gene Associated with Insensitivity to Arginine Vasopressin in Human Preeclamptic Placental Vasculature

Abstract

Background: Preeclampsia is one leading cause of maternal mortality and morbidity. Although the exact mechanisms that cause preeclampsia remain unclear, it is undeniable that the abnormal placental function and circulation is a center for initiation preeclampsia. As a potent vasoconstrictor, arginine vasopressin (AVP) has long been implicated in controlling placental vascular tone and circulation; its secretion is grossly elevated in preeclamptic circulation. However, little is known about the reactivity of AVP in preeclamptic placental vasculature. Methods: To reveal special features of placental vascular regulations with placental pathophysiological changes, as well as its molecular mechanisms under preeclamptic conditions, vascular functional and molecular assays were conducted with placental vessel samples from normal and preeclamptic pregnancies. Findings: Present study found that the vasoconstriction responses of placental vessels to AVP were attenuated in preeclampsia compared to 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, PKCB gene), particularly a hyper-methylation-mediated AVPR1A and PKCB gene downregulation, respectively. Interpretation: These findings collectively revealed that aberrant DNA methylation-mediated gene expressions are correlated with vascular dysfunction in preeclamptic placental circulation. Fund: This work was supported by National Nature & Science Foundation of China (81741024, 81873841, 81401244, 81771592 and 81320108006), the Natural Science Foundation of Jiangsu Province (BK20140292), and the Jiangsu Province's Shuang Chuang Tuan Dui and Key Discipline Fetal medicine. Declaration of Interest: All authors have no competing interests to declare, financial or otherwise. Ethical Approval: The Ethics committee of First Hospital of Soochow University approved all procedures in this work (no.2016-221), and all participants were given informed consent, conformed to the principles outlined in the Declaration of Helsinki.