Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics

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 pregnanc...

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Autores: 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, Diaz Ricart, M. Isabel, Gratacós Solsona, Eduard, Crispi Brillas, Fàtima
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/177018
Acceso en línea:https://hdl.handle.net/2445/177018
Access Level:acceso abierto
Palabra clave:Preeclàmpsia
Mort del fetus
Preeclampsia
Fetal death
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spelling Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomicsYoussef, LinaMiranda, JezidBlasco, MiquelPaules, CristinaCrovetto, FrancescaPalomo, MartaTorramade Moix, SergiGarcía Calderó, HéctorTura-Ceide, OlgaDantas, Ana PaulaHernández Gea, VirginiaHerrero, PolCanela i Canela, NúriaCampistol Plana, Josep M.Garcia Pagan, Joan CarlesDiaz Ricart, M. IsabelGratacós Solsona, EduardCrispi Brillas, FàtimaPreeclàmpsiaMort del fetusPreeclampsiaFetal deathPreeclampsia 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.Nature Publishing Group2021202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfhttps://hdl.handle.net/2445/177018Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41598-021-82733-zScientific Reports, 2021, vol. 11, num. 1, p. 3048https://doi.org/10.1038/s41598-021-82733-zcc-by (c) Youssef, Lina et al., 2021http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1770182026-05-29T05:05:01Z
dc.title.none.fl_str_mv Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics
title Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics
spellingShingle Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics
Youssef, Lina
Preeclàmpsia
Mort del fetus
Preeclampsia
Fetal death
title_short Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics
title_full Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics
title_fullStr Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics
title_full_unstemmed Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics
title_sort Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics
dc.creator.none.fl_str_mv 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
Diaz Ricart, M. Isabel
Gratacós Solsona, Eduard
Crispi Brillas, Fàtima
author Youssef, Lina
author_facet 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
Diaz Ricart, M. Isabel
Gratacós Solsona, Eduard
Crispi Brillas, Fàtima
author_role author
author2 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
Diaz Ricart, M. Isabel
Gratacós Solsona, Eduard
Crispi Brillas, Fàtima
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Preeclàmpsia
Mort del fetus
Preeclampsia
Fetal death
topic Preeclàmpsia
Mort del fetus
Preeclampsia
Fetal death
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/177018
url https://hdl.handle.net/2445/177018
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41598-021-82733-z
Scientific Reports, 2021, vol. 11, num. 1, p. 3048
https://doi.org/10.1038/s41598-021-82733-z
dc.rights.none.fl_str_mv cc-by (c) Youssef, Lina et al., 2021
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Youssef, Lina et al., 2021
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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