Altered expression of norepinephrine transporter and norepinephrine in human placenta cause pre-eclampsia through regulated trophoblast invasion

Abstract

ObjectiveWe investigated the norepinephrine transporter (NET) expression in normal and pre-eclamptic placentas and analyzed the invasion activity of trophoblastic cells based on norepinephrine (NE)-NET regulation.MethodsNET and NE expression levels were examined by western blot and enzyme-linked immunosorbent assay, respectively. Trophoblast invasion activity, depending on NE-NET regulation, was determined by NET-small interfering RNA (siRNA) and NET transfection into the human extravillous trophoblast cells with or without NE treatment and invasion rates were analyzed by zymography and an invasion assay.ResultsNET mRNA was expressed at a low level in pre-eclamptic placentas compared with normal placentas and NE concentration in maternal plasma increased significantly in pre-eclamptic women compared to normal pregnant women (p<0.05). NET gene upregulation and NE treatment stimulated trophoblast cell invasion up to 2.5-fold (p<0.05) by stimulating matrix metalloproteinase-9 activity via the phosphoinositol-3-kinase/AKT signaling pathway, whereas NET-siRNA with NE treatment reduced invasion rates.ConclusionNET expression is reduced by inadequate regulation of NE levels during placental development. This suggests that a complementary balance between NET and NE regulates trophoblast cell invasion activities during placental development.

Dopamine in the Pathophysiology of Preeclampsia and Gestational Hypertension: Monoamine Oxidase (MAO) and Catechol-O-methyl Transferase (COMT) as Possible Mechanisms

“…A study conducted by Na et al reported a reduced NET mRNA expression in preeclamptic placentas compared with normal placentas. More interestingly, they also observed that maternal plasma NE concentration was increased in preeclamptic women compared to normal pregnant women [77]. Similar findings were observed by Lampinen et al, who also noted an increase in plasma levels of norepinephrine in women with a previous history of PE [78].…”

A Comparative Study of Bolus Norepinephrine, Phenylephrine, and Ephedrine for the Treatment of Maternal Hypotension in Parturients with Preeclampsia During Cesarean Delivery Under Spinal Anesthesia

“…However, before this study, the feasibility of norepinephrine had not been explored for women with preeclampsia with uteroplacental insufficiency. Na et al [22] compared maternal norepinephrine in pregnant women with preeclampsia and normotensive pregnant women and found that parturients with preeclampsia had prominently increased levels of norepinephrine, raising the concern regarding whether women with preeclampsia would remain sensitive to exogenous norepinephrine. In this study, intermittent boluses were applied rather than the continuous infusion of norepinephrine or ephedrine to rescue spinal hypotension.…”

Comparison of efficacy of low-dose norepinephrine infusion with low-dose boluses of norepinephrine in managing hypotension among parturients undergoing caesarean section under the subarachnoid block

“…This finding raised questions about whether these women would still be sensitive to exogenous norepinephrine. 17 According to a study by Minzter et al in 2010, Norepinephrine had no impact on the fetal arterial perfusion pressure, and the fetoplacental microcirculation was unaffected. 18 In a study, Left Uterine Displacement (LUD) was not given post-administration of spinal anesthesia.…”