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Página principal > Artículos > Artículos publicados > Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics |
Fecha: | 2021 |
Resumen: | Preeclampsia is a pregnancy-specific multisystem disorder and a leading cause of maternal and perinatal morbidity and mortality. The exact pathogenesis of this multifactorial disease remains poorly defined. We applied proteomics analysis on maternal blood samples collected from 14 singleton pregnancies with early-onset severe preeclampsia and 6 uncomplicated pregnancies to investigate the pathophysiological pathways involved in this specific subgroup of preeclampsia. Maternal blood was drawn at diagnosis for cases and at matched gestational age for controls. LC-MS/MS proteomics analysis was conducted, and data were analyzed by multivariate and univariate statistical approaches with the identification of differential pathways by exploring the global human protein-protein interaction network. The unsupervised multivariate analysis (the principal component analysis) showed a clear difference between preeclamptic and uncomplicated pregnancies. The supervised multivariate analysis using orthogonal partial least square discriminant analysis resulted in a model with goodness of fit (RX = 0. 99, p < 0. 001) and a strong predictive ability (QY = 0. 8, p < 0. 001). By univariate analysis, we found 17 proteins statistically different after 5% FDR correction (q-value < 0. 05). Pathway enrichment analysis revealed 5 significantly enriched pathways whereby the activation of the complement and coagulation cascades was on top (p = 3. 17e−07). To validate these results, we assessed the deposits of C5b-9 complement complex and on endothelial cells that were exposed to activated plasma from an independent set of 4 cases of early-onset severe preeclampsia and 4 uncomplicated pregnancies. C5b-9 and Von Willbrand factor deposits were significantly higher in early-onset severe preeclampsia. Future studies are warranted to investigate potential therapeutic targets for early-onset severe preeclampsia within the complement and coagulation pathway. |
Ayudas: | Fundació la Marató de TV3 202026 Fundació la Marató de TV3 CP17/00114 "la Caixa" Foundation LCF/PR/GN14/10270005 "la Caixa" Foundation LCF/PR/GN18/10310003 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR1531 Ministerio de Economía y Competitividad PI14/00226 Ministerio de Economía y Competitividad PI17/00675 Instituto de Salud Carlos III PI18/00073 Ministerio de Economía y Competitividad PIE15/00027 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: | Adult ; Biomarkers ; Blood Coagulation ; Chromatography, Liquid ; Complement System Proteins ; Endothelial Cells ; Female ; Gestational Age ; Humans ; Pre-Eclampsia ; Pregnancy ; Proteomics ; Tandem Mass Spectrometry |
Publicado en: | Scientific reports, Vol. 11 Núm. 1 (december 2021) , p. 3048, ISSN 2045-2322 |
13 p, 2.3 MB |