Author:
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.
Abstract
AbstractAnimal 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.
Funder
H2020 Marie Skłodowska-Curie Actions
Bundesministerium für Bildung und Forschung
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Publisher
Springer Science and Business Media LLC
Cited by
10 articles.
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