Bioactive lipid mediators in plasma are predictors of preeclampsia irrespective of aspirin therapy |
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Affiliation: | 1. Division of Hematology & Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA;2. Department of Biochemistry and Molecular Biology, Virginia Commonwealth University (VCU), Richmond, VA, USA;3. Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, USA;4. Virginia Institute for Psychiatric & Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA;5. Division of Biostatistics, The Ohio State University College of Public Health, Columbus, OH, USA;6. Department of Cell Biology, University of Virginia, Charlottesville, VA, USA;7. Program in Cancer Biology, University of Virginia Cancer Center, Charlottesville, VA, USA;8. Research Service, Richmond Veterans Administration Medical Center, Richmond, VA, USA |
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Abstract: | There are few early biomarkers to identify pregnancies at risk of preeclampsia (PE) and abnormal placental function. In this cross-sectional study, we utilized targeted ultra-performance liquid chromatography-ESI MS/MS and a linear regression model to identify specific bioactive lipids that serve as early predictors of PE. Plasma samples were collected from 57 pregnant women prior to 24-weeks of gestation with outcomes of either PE (n = 26) or uncomplicated term pregnancies (n = 31), and the profiles of eicosanoids and sphingolipids were evaluated. Significant differences were revealed in the eicosanoid, (±)11,12 DHET, as well as multiple classes of sphingolipids; ceramides, ceramide-1-phosphate, sphingomyelin, and monohexosylceramides; all of which were associated with the subsequent development of PE regardless of aspirin therapy. Profiles of these bioactive lipids were found to vary based on self-designated race. Additional analyses demonstrated that PE patients can be stratified based on the lipid profile as to PE with a preterm birth linked to significant differences in the levels of 12-HETE, 15-HETE, and resolvin D1. Furthermore, subjects referred to a high-risk OB/GYN clinic had higher levels of 20-HETE, arachidonic acid, and Resolvin D1 versus subjects recruited from a routine, general OB/GYN clinic. Overall, this study shows that quantitative changes in plasma bioactive lipids detected by ultra-performance liquid chromatography-ESI-MS/MS can serve as an early predictor of PE and stratify pregnant people for PE type and risk. |
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Keywords: | eicosanoids sphingolipids pregnancy aspirin ultra-high performance liquid chromatography electrospray ionization-MS/MS AA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0040" }," $$" :[{" #name" :" text" ," _" :" arachidonic acid C1P" },{" #name" :" keyword" ," $" :{" id" :" kwrd0050" }," $$" :[{" #name" :" text" ," _" :" ceramide-1-phosphates CER" },{" #name" :" keyword" ," $" :{" id" :" kwrd0060" }," $$" :[{" #name" :" text" ," _" :" ceramides DHET" },{" #name" :" keyword" ," $" :{" id" :" kwrd0070" }," $$" :[{" #name" :" text" ," _" :" dihydroxyeicosatrienoic acid EET" },{" #name" :" keyword" ," $" :{" id" :" kwrd0080" }," $$" :[{" #name" :" text" ," _" :" epoxyeicosatrienoic acid MonHex" },{" #name" :" keyword" ," $" :{" id" :" kwrd0090" }," $$" :[{" #name" :" text" ," _" :" monohexosylceramides PE" },{" #name" :" keyword" ," $" :{" id" :" kwrd0100" }," $$" :[{" #name" :" text" ," _" :" preeclampsia RvD1" },{" #name" :" keyword" ," $" :{" id" :" kwrd0110" }," $$" :[{" #name" :" text" ," _" :" Resolvin D1 S1P" },{" #name" :" keyword" ," $" :{" id" :" kwrd0120" }," $$" :[{" #name" :" text" ," _" :" sphingosine-1-phosphate So" },{" #name" :" keyword" ," $" :{" id" :" kwrd0130" }," $$" :[{" #name" :" text" ," _" :" sphingosine thromboxane UPLC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0150" }," $$" :[{" #name" :" text" ," _" :" ultra-performance liquid chromatography |
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