{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T03:17:28Z","timestamp":1776309448211,"version":"3.50.1"},"reference-count":30,"publisher":"Croatian Society for Medical Biochemistry and Laboratory Medicine","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biochem. med. (Online)"],"published-print":{"date-parts":[[2025,2,15]]},"abstract":"<jats:p>Introduction: Sphingolipids, essential to trophoblast and endothelial function, may impact inflammation in preeclampsia. However, their specific role in late-onset preeclampsia remains unclear. To address this research gap, we analyzed sphingolipid profiles in pregnancies at high risk for preeclampsia development to identify potential biomarkers and clarify their role in disease pathogenesis.\nMaterials and methods: We monitored 90 pregnant women at high risk for preeclampsia development across four gestational points. These women were later categorized into the group of women with high risk who did not develop preeclampsia (HRG) (70 women) or the preeclampsia group (PG) (20 women). Sphingolipids (sphingosine, sphinganine, sphingosine-1-phosphate (S1P), ceramides C16:0\/C24:0, and sphingomyelin C16:0) were quantified via liquid chromatography-tandem mass spectrometry.\nResults: Sphingolipid profiles revealed distinct patterns between groups. Concentrations of S1P in the HRG increased from the 1st trimester to delivery (P &lt; 0.001). We did not notice significant changes in S1P during pregnancy in the PG but compared with the HRG we found significantly lower concentrations at each test point from the 2nd trimester until delivery (P = 0.020, P = 0.013, P = 0.011, respectively). Ceramides C16:0 and C24:0 demonstrated significant increases over time in HRG (P &lt; 0.001, both). Sphingomyelin C16:0 increased significantly across pregnancy in both groups (P &lt; 0.001 in HRG and P = 0.006 in PG), with no significant differences between groups.\nConclusions: We identified S1P as a potential biomarker for late-onset preeclampsia, with lower concentrations observed in PG compared to HRG. Rising sphingomyelin concentrations in both cohorts might serve as a relevant cardiovascular risk indicator in pregnancies at high risk for preeclampsia.<\/jats:p>","DOI":"10.11613\/bm.2025.010708","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T07:09:38Z","timestamp":1739948978000},"page":"119-128","source":"Crossref","is-referenced-by-count":1,"title":["Unraveling sphingolipid dynamics in late-onset preeclampsia: insights from lipidomic analysis"],"prefix":"10.11613","volume":"35","author":[{"given":"Aleksandra","family":"Stefanovi\u0107","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Zeljkovic","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Gojkovic","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Antonic","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Vladimirov","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeljko","family":"Mikovic","sequence":"additional","affiliation":[{"name":"The Obstetrics and Gynecology Clinic \u201cNarodni Front\u201d, Belgrade, Serbia. Department of Obstetrics and Gynecology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Snezana","family":"Jovicic","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Vekic","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Munjas","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmina","family":"Ivanisevic","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Ardalic","sequence":"additional","affiliation":[{"name":"The Obstetrics and Gynecology Clinic \u201cNarodni Front\u201d, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milica","family":"Miljkovic-Trailovic","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Saric-Matutinovic","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4885","published-online":{"date-parts":[[2025,2,15]]},"reference":[{"key":"key20250219120925_r1","first-page":"e1","article-title":"ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia.","volume":"133","author":"The American College of Obstetricians and Gynecologists","year":"2019","journal-title":"Obstet Gynecol"},{"key":"key20250219120925_r2"},{"key":"key20250219120925_r3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41572-023-00417-6","article-title":"Pre-eclampsia.","volume":"9","author":"Dimitriadis","year":"2023","journal-title":"Nat Rev Dis Primers"},{"key":"key20250219120925_r4","doi-asserted-by":"crossref","first-page":"S907","DOI":"10.1016\/j.ajog.2020.09.047","article-title":"Syncytiotrophoblast stress in preeclampsia: the convergence point for multiple pathways.","volume":"226","author":"Redman","year":"2022","journal-title":"Am J Obstet Gynecol"},{"key":"key20250219120925_r5","doi-asserted-by":"crossref","first-page":"9.e1","DOI":"10.1016\/j.ajog.2015.08.003","article-title":"Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity.","volume":"213","author":"Redman","year":"2015","journal-title":"Am J Obstet Gynecol"},{"key":"key20250219120925_r6","doi-asserted-by":"crossref","first-page":"590","DOI":"10.3390\/metabo12070590","article-title":"Dissecting the roles of lipids in preeclampsia.","volume":"12","author":"Yang","year":"2022","journal-title":"Metabolites"},{"key":"key20250219120925_r7"},{"key":"key20250219120925_r8","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1093\/aje\/kwu145","article-title":"Maternal hyperlipidemia and the risk of preeclampsia: a meta-analysis.","volume":"180","author":"Spracklen","year":"2014","journal-title":"Am J Epidemiol"},{"key":"key20250219120925_r9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-800177-6.00001-3","article-title":"Lipidomics applications for discovering biomarkers of diseases in clinical chemistry.","volume":"313","author":"Zhao","year":"2014","journal-title":"Int Rev Cell Mol Biol"},{"key":"key20250219120925_r10","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1080\/15548627.2015.1034414","article-title":"Disruption of sphingolipid metabolism augments ceramide-induced autophagy in preeclampsia.","volume":"11","author":"Melland-Smith","year":"2015","journal-title":"Autophagy"},{"key":"key20250219120925_r11","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0157221","article-title":"Impairement of Angiogenic Sphingosine Kinase-1\/Sphingosine-1-Phosphate Receptors patway in Preeclampsia.","volume":"11","author":"Dobierzewska","year":"2016","journal-title":"PLoS One"},{"key":"key20250219120925_r12","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0175118","article-title":"Plasma cross-gestational sphingolipidomic analyses reveal potential first trimester biomarkers of preeclampsia.","volume":"12","author":"Dobierzewska","year":"2017","journal-title":"PLoS One"},{"key":"key20250219120925_r13","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/s41419-018-0360-0","article-title":"Ceramide-induced BOK promotes mitochondrial fission in preeclampsia.","volume":"9","author":"Ausman","year":"2018","journal-title":"Cell Death Dis"},{"key":"key20250219120925_r14","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.3390\/ijms21031019","article-title":"Sphingolipid signature of human feto-placental vasculature in preeclampsia.","volume":"21","author":"Del Gaudio","year":"2020","journal-title":"Int J Mol Sci"},{"key":"key20250219120925_r15","doi-asserted-by":"crossref","first-page":"H2045","DOI":"10.1152\/ajpheart.01089.2002","article-title":"Sphingosine 1-phosphate and control of vascular tone.","volume":"284","author":"Dantas","year":"2003","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"key20250219120925_r16","unstructured":"National Institute of Health and Excellence. Quality standard [QS35]: Hypertension in pregnancy [Internet]. 2013 [cited 2024 Jan 15]. Available from: https:\/\/www.nice.org.uk\/guidance\/qs35\/resources\/hypertension-in-pregnancy-pdf-2098607923141"},{"key":"key20250219120925_r17","first-page":"16144","article-title":"Cholesterol homeostasis is dysregulated in women with preeclampsia.","volume":"131","author":"Antoni\u0107","year":"2021","journal-title":"Pol Arch Intern Med"},{"key":"key20250219120925_r18","doi-asserted-by":"crossref","first-page":"11357","DOI":"10.3390\/ijms241411357","article-title":"Cholesterol Metabolic Profiling of HDL in Women with Late-Onset Preeclampsia.","volume":"24","author":"Antoni\u0107","year":"2023","journal-title":"Int J Mol Sci"},{"key":"key20250219120925_r19"},{"key":"key20250219120925_r20","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences.","volume":"39","author":"Faul","year":"2007","journal-title":"Behav Res Methods"},{"key":"key20250219120925_r21","doi-asserted-by":"crossref","DOI":"10.1016\/j.jlr.2022.100312","article-title":"Plasma S1P and sphingosine are not different prior to pre-eclampsia in women at high risk of developing the Disease.","volume":"64","author":"Johnstone","year":"2023","journal-title":"J Lipid Res"},{"key":"key20250219120925_r22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0177601","article-title":"Sphingolipids as a new factor in the pathomechanism of preeclampsia - mass spectrometry analysis.","volume":"12","author":"Charkiewicz","year":"2017","journal-title":"PLoS One"},{"key":"key20250219120925_r23","article-title":"Preeclampsia is associated with changes in the composition and dysfunction of high-density lipoproteins.","volume":"11","author":"Picot","year":"2019","journal-title":"Arch Cardiovasc Dis Suppl"},{"key":"key20250219120925_r24","doi-asserted-by":"crossref","first-page":"44645","DOI":"10.1074\/jbc.M112.423426","article-title":"Sphingosine 1-phosphate (S1P) carrier-dependent regulation of endothelial barrier: high density lipoprotein (HDL)-S1P prolongs endothelial barrier enhancement as compared with albumin-S1P via effects on levels, trafficking, and signaling of S1P1.","volume":"287","author":"Wilkerson","year":"2012","journal-title":"J Biol Chem"},{"key":"key20250219120925_r25","article-title":"Sphingolipids in HDL\u2013Potential markers for adaptation to pregnancy?","volume":"1866","author":"Patanapirunhakit","year":"2021","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"key20250219120925_r26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.3389\/fphar.2015.00243","article-title":"HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications.","volume":"6","author":"Levkau","year":"2015","journal-title":"Front Pharmacol"},{"key":"key20250219120925_r27","doi-asserted-by":"crossref","first-page":"6273","DOI":"10.3390\/ijms20246273","article-title":"Novel insights into the role of HDL-associated sphingosine-1-phosphate in cardiometabolic diseases.","volume":"20","author":"Diarte-A\u00f1azco","year":"2019","journal-title":"Int J Mol Sci"},{"key":"key20250219120925_r28","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellsig.2021.110041","article-title":"Physiological and pathological functions of sphingolipids in pregnancy.","volume":"85","author":"Fakhr","year":"2021","journal-title":"Cell Signal"},{"key":"key20250219120925_r29","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.preghy.2019.12.006","article-title":"Plasma ceramide is increased and associated with proteinuria in women with pre-eclampsia and HELLP syndrome.","volume":"19","author":"Amraoui","year":"2020","journal-title":"Pregnancy Hypertens"},{"key":"key20250219120925_r30","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0110747","article-title":"Lipidomic assessment of plasma and placenta of women with early-onset preeclampsia.","volume":"9","author":"Korkes","year":"2014","journal-title":"PLoS One"}],"container-title":["Biochemia medica"],"original-title":[],"link":[{"URL":"https:\/\/biochemia-medica.com\/en\/journal\/35\/1\/10.11613\/BM.2025.010708\/fullArticle","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T08:29:51Z","timestamp":1761553791000},"score":1,"resource":{"primary":{"URL":"https:\/\/biochemia-medica.com\/en\/journal\/35\/1\/10.11613\/BM.2025.010708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,15]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,2,20]]},"published-print":{"date-parts":[[2025,2,15]]}},"URL":"https:\/\/doi.org\/10.11613\/bm.2025.010708","relation":{},"ISSN":["1846-7482","1330-0962"],"issn-type":[{"value":"1846-7482","type":"electronic"},{"value":"1330-0962","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2,15]]}}}