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Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe
Lina Youssef1, Jezid Miranda1, Miquel Blasco2
1BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Insights
Early-onset severe preeclampsia involves distinct protein differences, particularly in complement and coagulation pathways. These findings highlight potential therapeutic targets for this serious pregnancy complication.
Area of Science:
- Proteomics
- Maternal-Fetal Medicine
- Immunology
Background:
- Preeclampsia is a severe pregnancy disorder impacting maternal and fetal health.
- The underlying causes of preeclampsia, especially early-onset severe forms, are not fully understood.
Purpose of the Study:
- To investigate the proteomic differences in maternal blood from early-onset severe preeclampsia cases.
- To identify pathophysiological pathways implicated in this preeclampsia subgroup.
Main Methods:
- Proteomics analysis (LC-MS/MS) of maternal blood from preeclamptic and uncomplicated pregnancies.
- Multivariate and univariate statistical analyses to identify differential proteins and pathways.
- Validation of complement pathway activation using C5b-9 and Von Willebrand factor deposits.
Main Results:
- Proteomics revealed significant differences between preeclamptic and uncomplicated pregnancies.
- Seventeen proteins were statistically different, with complement and coagulation cascades identified as key activated pathways.
- Elevated C5b-9 and Von Willebrand factor deposits confirmed complement activation in early-onset severe preeclampsia.
Conclusions:
- Early-onset severe preeclampsia is characterized by distinct proteomic profiles, notably involving complement and coagulation pathways.
- These pathways represent potential therapeutic targets for early-onset severe preeclampsia.
- Further research is needed to explore therapeutic interventions within these identified pathways.
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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