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

摘要

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 biology Placental vascular dysfunction Pre-eclampsia.