Authors:	Pallares Robles, Alejandro ten Cate, Vincent Schulz, Andreas Prochaska, Jürgen H. Rapp, Steffen Koeck, Thomas Panova-Noeva, Marina Heitmeier, Stefan Schwers, Stephan Leineweber, Kirsten Seyfarth, Hans-Jürgen Opitz, Christian F. Spronk, Henri Espinola-Klein, Christine Lackner, Karl J. Münzel, Thomas Andrade-Navarro, Miguel A. Konstantinides, Stavros V. ten Cate, Hugo Wild, Philipp S.
Title:	Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis
Online publication date:	10-Feb-2023
Year of first publication:	2022
Language:	english
Abstract:	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 (n = 549) and 12-months after (n = 187). Among 444 proteins investigated, N = 21 and N = 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.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8797
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Scientific reports 12
Pages or article number:	9761
Publisher:	Macmillan Publishers Limited, part of Springer Nature
Publisher place:	London
Issue date:	2022
ISSN:	2045-2322
Publisher DOI:	10.1038/s41598-022-13174-5
Appears in collections:	DFG-491381577-G