Bioactive lipid mediators in plasma are predictors of preeclampsia irrespective of aspirin therapy

• Published in: Journal of lipid research Vol. 64; no. 6; p. 100377
• Main Authors: Stephenson, Daniel J., MacKnight, H. Patrick, Hoeferlin, L. Alexis, Washington, Sonya L., Sawyers, Chelsea, Archer, Kellie J., Strauss, Jerome F., Walsh, Scott W., Chalfant, Charles E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2023; American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: aspirin; Aspirin - therapeutic use; Biomarkers; Cross-Sectional Studies; Eicosanoids; Female; Humans; Infant, Newborn; Patient-oriented and Epidemiological Research; Placenta; Pre-Eclampsia; Pregnancy; Premature Birth; Sphingolipids; Tandem Mass Spectrometry; ultra-high performance liquid chromatography electrospray ionization-MS/MS; AA; C1P; sphingolipids; pregnancy; eicosanoids; CER; DHET; S1P; TXB2; EET; PE; UPLC; RvD1; aspirin; MonHex; So; ultra-high performance liquid chromatography electrospray ionization-MS/MS
• ISSN: 0022-2275; 1539-7262; 1539-7262
• DOI: 10.1016/j.jlr.2023.100377

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.