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,Hernandez-Gea Virginia,Herrero Pol,Canela Nuria,Campistol Josep Maria,Garcia-Pagan Joan Carles,Diaz-Ricart Maribel,Gratacos Eduard,Crispi Fatima
Abstract
AbstractPreeclampsia 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.
Funder
Erasmus Programme
Miguel Servet grant from the Instituto de Salud Carlos III
Instituto de Salud Carlos III
“la Caixa” Foundation
Cerebra Foundation
AGAUR 2017 SGR
Publisher
Springer Science and Business Media LLC
Cited by
25 articles.
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