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    • Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism 

      Iglesias, Maria Jesus; Sanchez-Rivera, Laura; Ibrahim-Kosta, Manal; Naudin, Clément; Munsch, Gaëlle; Goumidi, Louisa; Farm, Maria; Smith, Philip M.; Thibord, Florian; Kral-Pointner, Julia Barbara; Hong, Mun-Gwan; Suchon, Pierre; Germain, Marine; Schottmaier, Waltraud; Dusart, Philip James; Boland, Anne; Kotol, David; Edfors, Fredrik; Koprulu, Mine; Pietzner, Maik; Langenberg, Claudia; Damrauer, Scott M.; Johnson, Andrew D.; Klarin, Derek M.; Smith, Nicholas L.; Smadja, David M.; Holmström, Margareta; Magnusson, Maria; Silveira, Angela; Uhlén, Mathias; Renné, Thomas; Martinez-Perez, Angel; Emmerich, Joseph; Deleuze, Jean-Francois; Antovic, Jovan; Soria Fernandez, Jose Manuel; Assinger, Alice; Schwenk, Jochen M.; Souto Andres, Joan Carles; Morange, Pierre-Emmanuel; Butler, Lynn; Trégouët, David-Alexandre; Odeberg, Jacob (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-07)
      Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement ...

    • Identification of Endothelial Proteins in Plasma Associated With Cardiovascular Risk Factors 

      Butler, Lynn; Iglesias, Maria J.; Kruse, Larissa D.; Sanchez-Rivera, Laura; Enge, Linnea; Dusart, Philip; Hong, Mun-Gwan; Uhlén, Mathias; Renné, Thomas; Schwenk, Jochen M.; Bergstrom, Göran; Odeberg, Jacob (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-10-28)
      <b>Objective:</b> Endothelial cell (EC) dysfunction is a well-established response to cardiovascular disease risk factors, such as smoking and obesity. Risk factor exposure can modify EC signaling and behavior, leading to arterial and venous disease development. Here, we aimed to identify biomarker panels for the assessment of EC dysfunction, which could be useful for risk stratification or to monitor ...

    • Identification of the factor XII contact activation site enables sensitive coagulation diagnostics 

      Heestermans, Marco; Naudin, Clement; Mailer, Reiner K.; Konrath, Sandra; Klaetschke, Kristin; Jämsä, Anne; Frye, Maike; Deppermann, Carsten; Pula, Giordano; Kuta, Piotr; Friese, Manuel A.; Gelderblom, Mathias; Sickmann, Albert; Preston, Roger J. S.; Nofer, Jerzy-Roch; Rose-John, Stefan; Butler, Lynn; Salomon, Ophira; Stavrou, Evi X.; Renné, Thomas (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-09-22)
      Contact activation refers to the process of surface-induced activation of factor XII (FXII), which initiates blood coagulation and is captured by the activated partial thromboplastin time (aPTT) assay. Here, we show the mechanism and diagnostic implications of FXII contact activation. Screening of recombinant FXII mutants identified a continuous stretch of residues Gln317–Ser339 that was essential ...

    • Intrinsic coagulation pathway-mediated thrombin generation in mouse whole blood 

      Konrath, Sandra; Mailer, Reiner K.; Beerens, Manu; Englert, Hanna; Frye, Maike; Kuta, Piotr; Preston, Roger J. S.; Maas, Coen; Butler, Lynn; Roest, Mark; de Laat, Bas; Renné, Thomas (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-11-28)
      Calibrated Automated Thrombography (CAT) is a versatile and sensitive method for analyzing coagulation reactions culminating in thrombin generation (TG). Here, we present a CAT method for analyzing TG in murine whole blood by adapting the CAT assay used for measuring TG in human plasma. The diagnostically used artificial and physiologic factor XII (FXII) contact activators kaolin, ellagic acid ...

    • Targeting NETs using dual-active DNase1 variants 

      Englert, Hanna; Göbel, Josephine; Khong, Danika; Omidi, Maryam; Wolska, Nina; Konrath, Sandra; Frye, Maike; Mailer, Reiner K.; Beerens, Manu; Gerwers, Julian C.; Preston, Roger J. S.; Odeberg, Jacob; Butler, Lynn; Maas, Coen; Stavrou, Evi X.; Fuchs, Tobias A.; Renné, Thomas (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-05-23)
      Background: Neutrophil Extracellular Traps (NETs) are key mediators of immunothrombotic mechanisms and defective clearance of NETs from the circulation underlies an array of thrombotic, inflammatory, infectious, and autoimmune diseases. Efficient NET degradation depends on the combined activity of two distinct DNases, DNase1 and DNase1-like 3 (DNase1L3) that preferentially digest double-stranded DNA ...

    • Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate 

      Mailer, Reiner K.; Allende, Mikel; Heestermans, Marco; Schweizer, Michaela; Deppermann, Carsten; Frye, Maike; Pula, Giordano; Odeberg, Jacob Olof; Gelderblom, Mathias; Rose-John, Stefan; Sickmann, Albert; Blankenberg, Stefan; Huber, Tobias B.; Kubisch, Christian; Maas, Coen; Gambaryan, Stepan; Firsov, Dmitri; Stavrou, Evi X.; Butler, Lynn; Renné, Thomas (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-15)
      Polyphosphate is a procoagulant inorganic polymer of linear-linked orthophosphate residues. Multiple investigations have established the importance of platelet polyphosphate in blood coagulation; however, the mechanistic details of polyphosphate homeostasis in mammalian species remain largely undefined. In this study, xenotropic and polytropic retrovirus receptor 1 (XPR1) regulated polyphosphate in ...