ArticleCirculation2012
Cytochrome P450 subfamily 2J polypeptide 2 expression and circulating epoxyeicosatrienoic metabolites in preeclampsia.
Article in Circulation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Reduced uterine perfusion pressure as a model for preeclampsia and fetal growth restriction in murine: a systematic review and meta-analysis.American journal of physiology. Heart and circulatory physiology · 2024Pooled it
- Trial
- First-trimester plasma targeted metabolomics for eicosanoids reveals predictive potential and preventive targets for severe preeclampsia: a nested case-control study.BMC pregnancy and childbirth · 2026Article
- Placental CYP450 gene dysregulation by maternal PFAS: a novel mechanism linking prenatal exposure to altered toddler growth.Environmental health : a global access science source · 2026Article
- Associations between prenatal per- and polyfluoroalkyl substances (PFAS) and repeated measures of bioactive lipids during pregnancy in the LIFECODES cohort.The Science of the total environment · 2026Article
- ERV3-MLT1 provides cis-regulatory elements for human placental functioning and are commonly dysregulated in human-specific preeclampsia.Genome biology · 2025Article
- Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts.Environmental science & technology · 2024Article
- Cross-sectional associations between prenatal maternal per- and poly-fluoroalkyl substances and bioactive lipids in three Environmental influences on Child Health Outcomes (ECHO) cohorts.medRxiv : the preprint server for health sciences · 2023Article
- CD39 abrogates platelet-derived factors induced IL-1β expression in the human placenta.Frontiers in cell and developmental biology · 2023Article
- Expression of CYP450 enzymes in human fetal membranes and its implications in xenobiotic metabolism during pregnancy.Life sciences · 2022Article
- Orally active epoxyeicosatrienoic acid analogs in hypertension and renal injury.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Cyp2c44 epoxygenase-derived epoxyeicosatrienoic acids in vascular smooth muscle cells elicit vasoconstriction of the murine ophthalmic artery.Scientific reports · 2021Article
- Regulation of cardiovascular biology by microsomal epoxide hydrolase.Toxicological research · 2021Review
- Association of the sEH gene promoter polymorphisms and haplotypes with preeclampsia.Journal of medical biochemistry · 2020Article
- Unique features and emerging in vitro models of human placental development.Reproductive medicine and biology · 2020Review
- Prediction and associations of preterm birth and its subtypes with eicosanoid enzymatic pathways and inflammatory markers.Scientific reports · 2019Article
- Disturbed Cardiorespiratory Adaptation in Preeclampsia: Return to Normal Stress Regulation Shortly after Delivery?International journal of molecular sciences · 2019Article
- Increased Soluble Epoxide Hydrolase in Human Gestational Tissues from Pregnancies Complicated by Acute Chorioamnionitis.Mediators of inflammation · 2019Article
- Prospective for cytochrome P450 epoxygenase cardiovascular and renal therapeutics.Pharmacology & therapeutics · 2018Review
- Umbilical cord blood metabolomics reveal distinct signatures of dyslipidemia prior to bronchopulmonary dysplasia and pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2018Article
Corrections and comments
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Authors and funding
24 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPreeclampsia is a multisystem disorder of pregnancy, originating in the placenta. Cytochrome P450 (CYP)-dependent eicosanoids regulate vascular function, inflammation, and angiogenesis, which are mechanistically important in preeclampsia. METHODS AND
resultsWe performed microarray screening of placenta and decidua (maternal placenta) from 25 preeclamptic women and 23 control subjects. The CYP subfamily 2J polypeptide 2 (CYP2J2) was upregulated in preeclamptic placenta and decidua. Reverse-transcription polymerase chain reaction confirmed the upregulation, and immunohistochemistry localized CYP2J2 in trophoblastic villi and deciduas at 12 weeks and term. The CYP2J2 metabolites, 5,6-epoxyeicosatrienoic acid (EET), 14,15-EET, and the corresponding dihydroxyeicosatrienoic acids, were elevated in preeclamptic women compared with controls in the latter two thirds of pregnancy and after delivery. Stimulating a trophoblast-derived cell line with the preeclampsia-associated cytokine tumor necrosis factor-α enhanced CYP2J2 gene and protein expression. In 2 independent rat models of preeclampsia, reduced uterine-perfusion rat and the transgenic angiotensin II rat, we observed elevated EET, dihydroxyeicosatrienoic acid, and preeclamptic features that were ameliorated by the CYP epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MsPPOH). Uterine arterial rings of these rats also dilated in response to MsPPOH. Furthermore, 5,6-EET could be metabolized to a thromboxane analog. In a bioassay, 5,6-EET increased the beating rate of neonatal cardiomyocytes. Blocking thromboxane synthesis reversed that finding and also normalized large-conductance calcium-activated potassium channel activity.
conclusionsOur data implicate CYP2J2 in the pathogenesis of preeclampsia and as a potential candidate for the disturbed uteroplacental remodeling, leading to hypertension and endothelial dysfunction.
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Registered trials
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