Lack of thromboxane synthase prevents hypertension and fetal growth restriction after high salt treatment during pregnancy
Journal
PLoS ONE
Journal Volume
11
Journal Issue
3
Pages
e0151617
Date Issued
2016
Author(s)
Abstract
Preeclampsia (PE) is a potentially fatal pregnancy-related hypertensive disorder characterized by poor placenta development that can cause fetal growth restriction. PEassociated pathologies, including thrombosis, hypertension, and impaired placental development, may result from imbalances between thromboxane A2 (TXA2) and prostacyclin. Low-dose aspirin, which selectively inhibits TXA2 production, is used to prevent highrisk PE. However, the role of TXA2 in aspirin-mediated protective effects in women with PE is not understood fully. In this study, we examined the role of prostanoids in PE using human samples and an induced PE mouse model. We demonstrated that the administration of salted drinking water (2.7% NaCl) to wild-type mice resulted in elevated placental TXA2 synthase (TXAS) and plasma TXA2, but not prostacyclin, levels, which was also found in our clinical PE placenta samples. The high salt-treated wild-type pregnant mice had shown unchanged maternal body weight, hypertension (MAP increase 15 mmHg), and decreased pup weight (?50%) and size (?24%), but these adverse effects were ameliorated in TXAS knockout (KO) mice. Moreover, increased expression of interleukin-1β and downstream phosphorylated-p38-mitogen-activated protein kinase were concordant with apoptosis induction in the placentas of salt water-treated wild-type mice. These alterations were not observed in TXAS KO mice. Together, our data suggest that TXA2 depletion has anti-PE effects due to the prevention of hypertension and placental damage through downregulation of the interleukin-1β pathway. ? 2016 Pai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Other Subjects
drinking water; interleukin 1beta; mitogen activated protein kinase p38; prostanoid; thromboxane synthase; chloride; interleukin 1beta; salt intake; sodium; thromboxane synthase; animal experiment; animal model; animal tissue; apoptosis; Article; blood level; body weight; controlled study; cytokine production; disease activity; disease association; enzyme activity; enzyme assay; female; fetus; hypertension; intrauterine growth retardation; molecular pathology; mouse; nonhuman; pregnancy; protein expression; salt intake; signal transduction; adverse effects; animal; Bagg albino mouse; blood; blood pressure; cell count; complication; drug effects; enzymology; Fetal Growth Retardation; human; hypertension; knockout mouse; male; metabolism; perfusion; phenotype; placenta; preeclampsia; upregulation; Animals; Apoptosis; Blood Pressure; Cell Count; Chlorides; Female; Fetal Growth Retardation; Humans; Hypertension; Interleukin-1beta; Male; Mice, Inbred BALB C; Mice, Knockout; Perfusion; Phenotype; Placenta; Pre-Eclampsia; Pregnancy; Signal Transduction; Sodium; Sodium Chloride, Dietary; Thromboxane-A Synthase; Up-Regulation
Type
journal article