The Interplay between Pathophysiological Pathways in Early-Onset Severe Preeclampsia Unveiled by Metabolomics
Por:
Youssef L, Crovetto F, Simoes RV, Miranda J, Paules C, Blasco M, Palomo M, García-Calderó H, Tura-Ceide O, Dantas AP, Hernandez-Gea V, Herrero P, Canela N, Campistol JM, Garcia-Pagan JC, Diaz-Ricart M, Gratacós E and Crispi F
Publicada:
1 ene 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 ((RX)-X-2 = 0.91, p = 0.002) and predictive ability (Q(2)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.
Filiaciones:
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BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Crovetto F:
BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Simoes RV:
BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Champalimaud Research, Champalimaud Centre for the Unknown, 1400-038 Lisbon, Portugal
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BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
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BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Blasco M:
Nephrology and Renal Transplantation Department, Hospital Clínic, Centro de Referencia en Enfermedad Glomerular Compleja del Sistema Nacional de Salud (CSUR), University of Barcelona, 08036 Barcelona, Spain
Palomo M:
Josep Carreras Leukaemia Research Institute, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
Hematopathology, Centre Diagnòstic Biomèdic (CDB), Hemotherapy-Hemostasis Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Barcelona Endothelium Team (BET), 08036 Barcelona, Spain
García-Calderó H:
Barcelona Hepatic Hemodynamics Laboratory, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), 08036 Barcelona, Spain
Tura-Ceide O:
Department of Pulmonary Medicine, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
Girona Biomedical Research Institute-IDIBGI, 17190 Girona, Spain
Dantas AP:
Cardiovascular Institute, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Hernandez-Gea V:
Barcelona Hepatic Hemodynamics Laboratory, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), 08036 Barcelona, Spain
Herrero P:
Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), 43204 Reus, Spain
Canela N:
Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), 43204 Reus, Spain
Campistol JM:
Nephrology and Renal Transplantation Department, Hospital Clínic, Centro de Referencia en Enfermedad Glomerular Compleja del Sistema Nacional de Salud (CSUR), University of Barcelona, 08036 Barcelona, Spain
Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, 28029 Madrid, Spain
Garcia-Pagan JC:
Barcelona Hepatic Hemodynamics Laboratory, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), 08036 Barcelona, Spain
Diaz-Ricart M:
Hematopathology, Centre Diagnòstic Biomèdic (CDB), Hemotherapy-Hemostasis Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Barcelona Endothelium Team (BET), 08036 Barcelona, Spain
Gratacós E:
BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, 28029 Madrid, Spain
Crispi F:
BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Déu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, 28029 Madrid, Spain
Green Submitted, gold
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