Abstract P310: Hypermethylation of Dlk1-meg3 Loci in Human Umbilical Veins: Insights Into Offspring Vasculardysfunction Born After Pre-Eclampsia

Abstract

Increasing epidemiological studies have confirmed the association between maternal pre-eclampsia and elevated blood pressure in their offspring. In our study, we explored the potential epigenetic regulation of Dlk1-Meg3 region in human umbilical vein endothelial cells, and its connection with endothelium-derived factors. We recruited 58 singletons born spontaneously and 67 singletons born with pre-eclampsia during 2016 to detect blood pressure and growth development index, and found that diastolic blood pressure was significantly lower in pre-eclampsia offspring who born over 34 weeks compared to normal offspring (53.59±1.38mmHg VS 59.9±1.40mmHg, P<0.01), which leads to higher pulse pressure difference. RT-qPCR showed that imprinted gene Dlk1 level significantly increased and Meg3 level decreased in HUVECs than that in control group, accompanying with lower expression of endothelial nitric oxide synthase(eNOS) and vascular endothelial growth factor (VEGF) , higher expression of endothelin-1 (ET1), which are close related with vascular endothelial function. Meanwhile, ELISA assay of ET1, Nitrite, VEGF were consistent with Real-time results. Besides, we used pyrosequencing to find that abnormal expression of Dlk1-Meg3 expression were caused by hyper-methylation status of IG-DMR. And methylation status of IG-DMR highly correlated with ET1 concentration and Nitrate concentration, these might be one of the mechanisms for impaired endothelial function (Coeffient=0.5806, P=0.0115; Coeffient=-0.4883, P=0.0398). Our results demonstrated that altered expression of imprinted gene Dlk1 and Meg3 were caused by hypermethylation of IG-DMR in pre-eclampsia HUVECs, accompanied by lower secretion of nitrite, VEGF, and higher secretion of ET1. It might be one potential mechanism for higher risk of cardiovascular disease in pre-eclampsia offspring later in life.