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Title: Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics
Author: Youssef, Lina
Miranda, Jezid
Blasco, Miquel
Paules, Cristina
Crovetto, Francesca
Palomo, Marta
Torramade Moix, Sergi
García Calderó, Héctor
Tura-Ceide, Olga
Dantas, Ana Paula
Hernández Gea, Virginia
Herrero, Pol
Canela i Canela, Núria
Campistol Plana, Josep M.
Garcia Pagan, Joan Carles
Díaz Ricart, Maribel
Gratacós Solsona, Eduard
Crispi Brillas, Fàtima
Keywords: Preeclàmpsia
Mort del fetus
Fetal death
Issue Date: 4-Feb-2021
Publisher: Nature Publishing Group
Abstract: 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 (R2X = 0.99, p < 0.001) and a strong predictive ability (Q2Y = 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.
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It is part of: Scientific Reports, 2021, vol. 11, num. 1, p. 3048
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ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
Articles publicats en revistes (BCNatal Fetal Medicine Research Center)

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