title: Lack of Thromboxane Synthase Prevents Hypertension and Fetal Growth Restriction after High Salt Treatment during Pregnancy.
abstract: Preeclampsia (PE) is a potentially fatal pregnancy-related hypertensive disorder characterized by poor placenta development that can cause fetal growth restriction. PE-associated 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 high-risk 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.
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chen-Hsueh
authors.initials: CH
authors.lastname: Pai
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ching-Tzu
authors.initials: CT
authors.lastname: Yen
authors.affiliation: Division of High Risk Pregnancy, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chie-Pein
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: I-Shing
authors.initials: IS
authors.lastname: Yu
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shu-Wha
authors.initials: SW
authors.lastname: Lin
authors.affiliation: Department of Bioscience Technology, College of Science, Chung-Yuan Christian University, Taoyuan, Taiwan.|Center for Nanotechnology and Center for Biomedical Technology, Chung-Yuan Christian University, Taoyuan, Taiwan.
authors.forename: Shu-Rung
authors.initials: SR
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002452:Cell Count; D002712:Chlorides / Q000097:blood; D005260:Female; D005317:Fetal Growth Retardation / Q000201:enzymology / Q000517:prevention & control*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000201:enzymology / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010477:Perfusion; D010641:Phenotype; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000097:blood / Q000201:enzymology; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013930:Thromboxane-A Synthase / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D002712:Chlorides; D053583:Interleukin-1beta; D017673:Sodium Chloride, Dietary; D012964:Sodium; D013930:Thromboxane-A Synthase