The Interplay between Pathophysiological Pathways in Early-Onset Severe Preeclampsia Unveiled by Metabolomics
Youssef, Lina (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Crovetto, Francesca (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Simoes, Rui Vasco (Champalimaud Research. Champalimaud Centre for the Unknown)
Miranda, Jezid (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Paules, Cristina (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Blasco Pelicano, Miquel (Hospital Clínic i Provincial de Barcelona)
Palomo, Marta (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
García Calderó, Héctor (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Tura-Ceide, Olga (Institut d'Investigació Biomèdica de Girona)
Dantas, A. P (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Hernández-Gea, Virginia (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Herrero, Pol (Eurecat. Centre Tecnològic de Catalunya)
Canela, Núria (Eurecat. Centre Tecnològic de Catalunya)
Campistol Plana, Josep M. (Hospital Clínic i Provincial de Barcelona)
Garcia Pagan, Joan Carles (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Diaz-Ricart, Maribel (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Gratacós, Eduard (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Crispi, Fatima (Centro de Investigación Biomédica en Red de Enfermedades Raras)

Fecha:	2022
Resumen:	Introduction: Preeclampsia is a multi-system disorder unique to pregnancy responsible for a great part of maternal and perinatal morbidity and mortality. The precise pathogenesis of this complex disorder is still unrevealed. Methods: We examined the pathophysiological pathways involved in early-onset preeclampsia, a specific subgroup representing its most severe presentation, using LC-MS/MS metabolomic analysis based on multi-level extraction of lipids and small metabolites from maternal blood samples, collected at the time of diagnosis from 14 preeclamptic and six matched healthy pregnancies. Statistical analysis comprised multivariate and univariate approaches with the application of over representation analysis to identify differential pathways. Results: A clear difference between preeclamptic and control pregnancies was observed in principal component analysis. Supervised multivariate analysis using orthogonal partial least square discriminant analysis provided a robust model with goodness of fit (R X = 0. 91, p = 0. 002) and predictive ability (Q Y = 0. 72, p < 0. 001). Finally, univariate analysis followed by 5% false discovery rate correction indicated 82 metabolites significantly altered, corresponding to six overrepresented pathways: (1) aminoacyl-tRNA biosynthesis; (2) arginine biosynthesis; (3) alanine, aspartate and glutamate metabolism; (4) D-glutamine and D-glutamate metabolism; (5) arginine and proline metabolism; and (6) histidine metabolism. Conclusion: Metabolomic analysis focusing specifically on the early-onset severe form of preeclampsia reveals the interplay between pathophysiological pathways involved in this form. Future studies are required to explore new therapeutic approaches targeting these altered metabolic pathways in early-onset preeclampsia.
Ayudas:	Instituto de Salud Carlos III JR19/00006 Instituto de Salud Carlos III CP17/00114 Ministerio de Economía y Competitividad PID2019-105/48RB-I00 Ministerio de Economía y Competitividad PI14/00226 Ministerio de Economía y Competitividad PI15/00130 Ministerio de Economía y Competitividad PIE15/00027 Instituto de Salud Carlos III PI17/00675 Instituto de Salud Carlos III PI18/00073 Instituto de Salud Carlos III PI18/00960 Instituto de Salud Carlos III PI19/00888 Instituto de Salud Carlos III PI20/00569
Nota:	Fundació Carreras
Nota:	Funding: This project has been partially funded with the support of the Erasmus+ Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use, which may be made of the information contained therein. Additionally, the research leading to these results has received funding form "la Caixa" Foundation under grant agreements LCF/PR/GN14/10270005 and LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI14/00226, PI15/00130, PIE15/00027, PI17/00675, PI18/00073, PI18/00960, PI19/00888, PI20/00569) integrados en el Plan Nacional de I+D+I y cofinanciados por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) "Una manera de hacer Europa", Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK), Ministerio de Economía y Competitividad (SAF PID2019-105/48RB-100), Fundació La Marató de TV3 (202026-10), Instituto Juan Carlos III (JR19/00006), European Reference Network (ERN) RARE-Liver (hepatic diseases) and AGAUR 2017 SGR grant nº 1531 and 517 from Generalitat de Catalunya. O.T.C. was supported by Miguel Servet grant from the Instituto de Salud Carlos III (CP17/00114).
Nota:	This project has been partially funded with the support of the Erasmus+ Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use, which may be made of the information contained therein. Additionally, the research leading to these results has received funding form "la Caixa" Foundation under grant agreements LCF/PR/GN14/10270005 and LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI14/00226, PI15/00130, PIE15/00027, PI17/00675, PI18/00073, PI18/00960, PI19/00888, PI20/00569) integrados en el Plan Nacional de I+D+I y cofinanciados por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) "Una manera de hacer Europa", Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK), Ministerio de Economía y Competitividad (SAF PID2019-105/48RB-100), Fundació La Marató de TV3 (202026-10), Instituto Juan Carlos III (JR19/00006), European Reference Network (ERN) RARE-Liver (hepatic diseases) and AGAUR 2017 SGR grant nº 1531 and 517 from Generalitat de Catalunya. O.T.C. was supported by Miguel Servet grant from the Instituto de Salud Carlos III (CP17/00114).
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Early-onset preeclampsia ; Fetal growth restriction ; LC-MS/MS ; Maternal serum ; Preeclampsia ; Metabolomics ; Severe preeclampsia
Publicado en:	Life, Vol. 12 Núm. 1 (january 2022) , p. 86, ISSN 2075-1729

DOI: 10.3390/life12010086
PMID: 35054479

21 p, 1.4 MB

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