Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis
- Publication type:
- Journal article
- Metadata:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:p>Animal experiments and early phase human trials suggest that inhibition of factor XIa (FXIa) safely prevents venous thromboembolism (VTE), and specific murine models of sepsis have shown potential efficacy in alleviating cytokine storm. These latter findings support the role of FXI beyond coagulation. Here, we combine targeted proteomics, machine learning and bioinformatics, to discover associations between FXI activity (FXI:C) and the plasma protein profile of patients with VTE. FXI:C was measured with a modified activated partial prothrombin time (APTT) clotting time assay. Proximity extension assay-based protein profiling was performed on plasma collected from subjects from the Genotyping and Molecular Phenotyping of Venous Thromboembolism (GMP-VTE) Project, collected during an acute VTE event (<jats:italic>n</jats:italic> = 549) and 12-months after (<jats:italic>n</jats:italic> = 187). Among 444 proteins investigated, <jats:italic>N</jats:italic> = 21 and <jats:italic>N</jats:italic> = 66 were associated with FXI:C during the acute VTE event and at 12 months follow-up, respectively. Seven proteins were identified as FXI:C-associated at both time points. These FXI-related proteins were enriched in immune pathways related to causes of thrombo-inflammation, extracellular matrix interaction, lipid metabolism, and apoptosis. The results of this study offer important new avenues for future research into the multiple properties of FXI, which are of high clinical interest given the current development of FXI inhibitors.</jats:p>
- Autoren
- Alejandro Pallares Robles
- Vincent ten Cate
- Andreas Schulz
- Jürgen H Prochaska
- Steffen Rapp
- Thomas Koeck
- Marina Panova-Noeva
- Stefan Heitmeier
- Stephan Schwers
- Kirsten Leineweber
- Hans-Jürgen Seyfarth
- Christian F Opitz
- Henri Spronk
- Christine Espinola-Klein
- Karl J Lackner
- Thomas Münzel
- Miguel A Andrade-Navarro
- Stavros V Konstantinides
- Hugo ten Cate
- Philipp S Wild
- DOI
- 10.1038/s41598-022-13174-5
- eISSN
- 2045-2322
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Scientific Reports
- Sprache
- en
- Artikelnummer
- 9761
- Online publication date
- 2022
- Status
- Published online
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1038/s41598-022-13174-5
- Datum der Datenerfassung
- 2022
- Titel
- Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis
- Ausgabe der Zeitschrift
- 12
Data source: Crossref
- Other metadata sources:
-
- Author's licence
- CC-BY
- Autoren
- Alejandro Pallares Robles
- Vincent ten Cate
- Andreas Schulz
- Jürgen H Prochaska
- Steffen Rapp
- Thomas Koeck
- Marina Panova-Noeva
- Stefan Heitmeier
- Stephan Schwers
- Kirsten Leineweber
- Hans-Jürgen Seyfarth
- Christian F Opitz
- Henri Spronk
- Christine Espinola-Klein
- Karl J Lackner
- Thomas Münzel
- Miguel A Andrade-Navarro
- Stavros V Konstantinides
- Hugo ten Cate
- Philipp S Wild
- Hosting institution
- Universitätsbibliothek Mainz
- Sammlungen
- DFG-491381577-G
- Resource version
- Published version
- DOI
- 10.1038/s41598-022-13174-5
- Funding acknowledgements
- Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577
- File(s) embargoed
- false
- Open access
- true
- ISSN
- 2045-2322
- Zeitschrift
- Scientific reports
- Schlüsselwörter
- 610 Medizin
- 610 Medical sciences
- Sprache
- eng
- Open access status
- Open Access
- Paginierung
- 9761
- Datum der Veröffentlichung
- 2022
- Public URL
- https://openscience.ub.uni-mainz.de/handle/20.500.12030/8813
- Herausgeber
- Macmillan Publishers Limited, part of Springer Nature
- Datum der Datenerfassung
- 2023
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2023
- Zugang
- Public
- Titel
- Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis
- Ausgabe der Zeitschrift
- 12
Files
association_of_fxi_activity_w-20230210104343752.pdf
Data source: OPENSCIENCE.UB