Advertisement

Subtype-specific plasma signatures of platelet-related protein releasate in acute pulmonary embolism

  • Gaukhar Baidildinova
    Affiliations
    Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands

    Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
    Search for articles by this author
  • Vincent ten Cate
    Affiliations
    Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
    Search for articles by this author
  • Markus Nagler
    Affiliations
    Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
    Search for articles by this author
  • Marina Panova-Noeva
    Affiliations
    Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
    Search for articles by this author
  • Steffen Rapp
    Affiliations
    Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
    Search for articles by this author
  • Thomas Köck
    Affiliations
    Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
    Search for articles by this author
  • Jürgen H. Prochaska
    Affiliations
    Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
    Search for articles by this author
  • Stefan Heitmeier
    Affiliations
    Division Pharmaceuticals, Bayer AG, Wuppertal, Germany
    Search for articles by this author
  • Christoph Gerdes
    Affiliations
    Division Pharmaceuticals, Bayer AG, Wuppertal, Germany
    Search for articles by this author
  • Stephan Schwers
    Affiliations
    Division Pharmaceuticals, Bayer AG, Wuppertal, Germany
    Search for articles by this author
  • Stavros V. Konstantinides
    Affiliations
    Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
    Search for articles by this author
  • Thomas Münzel
    Affiliations
    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany

    Department of Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
    Search for articles by this author
  • Christine Espinola-Klein
    Affiliations
    Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    Center for Cardiology, Cardiology III – Angiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany
    Search for articles by this author
  • Karl J. Lackner
    Affiliations
    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany

    Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
    Search for articles by this author
  • Henri M.N. Spronk
    Affiliations
    Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands

    Thrombosis Expertise Center, Heart and Vascular Center, Maastricht University Medical Center, Maastricht, Netherlands
    Search for articles by this author
  • Hugo ten Cate
    Affiliations
    Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands

    Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    Thrombosis Expertise Center, Heart and Vascular Center, Maastricht University Medical Center, Maastricht, Netherlands
    Search for articles by this author
  • Paola E.J. van der Meijden
    Affiliations
    Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands

    Thrombosis Expertise Center, Heart and Vascular Center, Maastricht University Medical Center, Maastricht, Netherlands
    Search for articles by this author
  • Kirsten Leineweber
    Affiliations
    Division Pharmaceuticals, Bayer AG, Wuppertal, Germany
    Search for articles by this author
  • Philipp S. Wild
    Affiliations
    Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
    Search for articles by this author
  • Kerstin Jurk
    Correspondence
    Corresponding author at: Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
    Affiliations
    Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
    Search for articles by this author

      Abstract

      Introduction

      There is evidence that plasma protein profiles differ in the two subtypes of pulmonary embolism (PE), isolated PE (iPE) and deep vein thrombosis (DVT)-associated PE (DVT-PE), in the acute phase. The aim of this study was to determine specific plasma signatures for proteins related to platelets in acute iPE and DVT-PE compared to isolated DVT (iDVT).

      Methods

      Within the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism (GMP-VTE) Project, a multicenter prospective cohort study of 693 confirmed VTE cases, a highly sensitive targeted proteomics approach based on dual-antibody proximity extension assay was applied. LASSO-regularized logistic regression analysis selected 33 and 30 of 135 platelet-related candidate proteins in iPE and DVT-PE vs. iDVT, respectively.

      Results

      All regulated proteins were well associated with six prominently released platelet proteins and the majority showed specificity for iPE and DVT-PE compared to iDVT. While iPE-specific proteins were assigned to be predominantly released via shedding mechanisms and extracellular vesicles, granule secretion was identified as a major release mechanism assigned to DVT-associated PE-specific proteins. Network analysis demonstrated three interconnected clusters of specifically regulated proteins in iPE linked to immunoreceptor signaling, pathogen clearance and chemotaxis, whereas for DVT-associated PE one cluster linked to tissue remodeling and leukocyte trafficking. Machine learning-based analysis reveals specific plasma signatures and differential release mechanisms of proteins related to platelets in acute iPE and DVT-associated PE.

      Conclusion

      These data suggest that the platelet protein releasate contributes to the differential regulation of plasma proteins in acute PE compared to iDVT, which may be associated with different platelet activation patterns.

      Graphical abstract

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Thrombosis Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Jackson S.P.
        Arterial thrombosis–insidious, unpredictable and deadly.
        Nat. Med. 2011; 17: 1423-1436
        • Stark K.
        • Massberg S.
        Interplay between inflammation and thrombosis in cardiovascular pathology.
        Nat. Rev. Cardiol. 2021; 18: 666-682
        • von Bruhl M.L.
        • Stark K.
        • Steinhart A.
        • Chandraratne S.
        • Konrad I.
        • Lorenz M.
        • Khandoga A.
        • Tirniceriu A.
        • Coletti R.
        • Kollnberger M.
        • Byrne R.A.
        • Laitinen I.
        • Walch A.
        • Brill A.
        • Pfeiler S.
        • Manukyan D.
        • Braun S.
        • Lange P.
        • Riegger J.
        • Ware J.
        • Eckart A.
        • Haidari S.
        • Rudelius M.
        • Schulz C.
        • Echtler K.
        • Brinkmann V.
        • Schwaiger M.
        • Preissner K.T.
        • Wagner D.D.
        • Mackman N.
        • Engelmann B.
        • Massberg S.
        Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo.
        J. Exp. Med. 2012; 209: 819-835
        • Becattini C.
        • Agnelli G.
        • Schenone A.
        • Eichinger S.
        • Bucherini E.
        • Silingardi M.
        • Bianchi M.
        • Moia M.
        • Ageno W.
        • Vandelli M.R.
        • Grandone E.
        • Prandoni P.
        • Investigators W.
        Aspirin for preventing the recurrence of venous thromboembolism.
        N. Engl. J. Med. 2012; 366: 1959-1967
        • Brighton T.A.
        • Eikelboom J.W.
        • Mann K.
        • Mister R.
        • Gallus A.
        • Ockelford P.
        • Gibbs H.
        • Hague W.
        • Xavier D.
        • Diaz R.
        • Kirby A.
        • Simes J.
        • Investigators A.
        Low-dose aspirin for preventing recurrent venous thromboembolism.
        N. Engl. J. Med. 2012; 367: 1979-1987
        • Simes J.
        • Becattini C.
        • Agnelli G.
        • Eikelboom J.W.
        • Kirby A.C.
        • Mister R.
        • Prandoni P.
        • Brighton T.A.
        • Investigators I.S.
        Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration.
        Circulation. 2014; 130: 1062-1071
        • Heestermans M.
        • Salloum-Asfar S.
        • Streef T.
        • Laghmani E.H.
        • Salvatori D.
        • Luken B.M.
        • Zeerleder S.S.
        • Spronk H.M.H.
        • Korporaal S.J.
        • Kirchhofer D.
        • Wagenaar G.T.M.
        • Versteeg H.H.
        • Reitsma P.H.
        • Renne T.
        • van Vlijmen B.J.M.
        Mouse venous thrombosis upon silencing of anticoagulants depends on tissue factor and platelets, not FXII or neutrophils.
        Blood. 2019; 133: 2090-2099
        • Panova-Noeva M.
        • Wagner B.
        • Nagler M.
        • Koeck T.
        • Ten Cate V.
        • Prochaska J.H.
        • Heitmeier S.
        • Meyer I.
        • Gerdes C.
        • Laux V.
        • Konstantinides S.
        • Spronk H.M.
        • Munzel T.
        • Lackner K.J.
        • Leineweber K.
        • Ten Cate H.
        • Wild P.S.
        Comprehensive platelet phenotyping supports the role of platelets in the pathogenesis of acute venous thromboembolism - results from clinical observation studies.
        EBioMedicine. 2020; 60102978
        • Perrella G.
        • Huang J.
        • Provenzale I.
        • Swieringa F.
        • Heubel-Moenen F.
        • Farndale R.W.
        • Roest M.
        • van der Meijden P.E.J.
        • Thomas M.
        • Ariens R.A.S.
        • Jandrot-Perrus M.
        • Watson S.P.
        • Heemskerk J.W.M.
        Nonredundant roles of platelet glycoprotein VI and integrin alphallbbeta3 in fibrin-mediated microthrombus formation.
        Arterioscler. Thromb. Vasc. Biol. 2021; 41: e97-e111
        • Golebiewska E.M.
        • Poole A.W.
        Platelet secretion: from haemostasis to wound healing and beyond.
        Blood Rev. 2015; 29: 153-162
        • Huang J.
        • Swieringa F.
        • Solari F.A.
        • Provenzale I.
        • Grassi L.
        • De Simone I.
        • Baaten C.
        • Cavill R.
        • Sickmann A.
        • Frontini M.
        • Heemskerk J.W.M.
        Assessment of a complete and classified platelet proteome from genome-wide transcripts of human platelets and megakaryocytes covering platelet functions.
        Sci. Rep. 2021; 11: 12358
        • Burkhart J.M.
        • Vaudel M.
        • Gambaryan S.
        • Radau S.
        • Walter U.
        • Martens L.
        • Geiger J.
        • Sickmann A.
        • Zahedi R.P.
        The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways.
        Blood. 2012; 120: e73-e82
        • Di Michele M.G.
        • Freson K.
        K., Platelet proteomics and its applications to study platelet-related disorders.
        in: Gresele P. Kleiman N.S. Lopez J.A. Page C.P. Platelets in Thrombotic and Non-Thrombotic Disorders. Springer International Publishing AG, Cham, Switzerland2017: 157-170
        • Furio E.
        • Garcia-Fuster M.J.
        • Redon J.
        • Marques P.
        • Ortega R.
        • Sanz M.J.
        • Piqueras L.
        CX3CR1/CX3CL1 axis mediates platelet-leukocyte adhesion to arterial endothelium in younger patients with a history of idiopathic deep vein thrombosis.
        Thromb. Haemost. 2018; 118: 562-571
        • Kyrle P.A.
        • Hron G.
        • Eichinger S.
        • Wagner O.
        Circulating P-selectin and the risk of recurrent venous thromboembolism.
        Thromb. Haemost. 2007; 97: 880-883
        • Ten Cate V.
        • Prochaska J.H.
        • Schulz A.
        • Koeck T.
        • Pallares Robles A.
        • Lenz M.
        • Eggebrecht L.
        • Rapp S.
        • Panova-Noeva M.
        • Ghofrani H.A.
        • Meyer F.J.
        • Espinola-Klein C.
        • Lackner K.J.
        • Michal M.
        • Schuster A.K.
        • Strauch K.
        • Zink A.M.
        • Laux V.
        • Heitmeier S.
        • Konstantinides S.V.
        • Munzel T.
        • Andrade-Navarro M.A.
        • Leineweber K.
        • Wild P.S.
        Protein expression profiling suggests relevance of noncanonical pathways in isolated pulmonary embolism.
        Blood. 2021; 137: 2681-2693
        • Cate V.Ten
        • Koeck T.
        • Panova-Noeva M.
        • Rapp S.
        • Prochaska J.H.
        • Lenz M.
        • Schulz A.
        • Eggebrecht L.
        • Hermanns M.I.
        • Heitmeier S.
        • Krahn T.
        • Laux V.
        • Munzel T.
        • Leineweber K.
        • Konstantinides S.V.
        • Wild P.S.
        • Collaborators F.B.S.
        Investigators, V.T. study, A prospective cohort study to identify and evaluate endotypes of venous thromboembolism: rationale and design of the Genotyping and Molecular Phenotyping in Venous Thrombo Embolism project (GMP-VTE).
        Thromb. Res. 2019; 181: 84-91
        • Assarsson E.
        • Lundberg M.
        • Holmquist G.
        • Bjorkesten J.
        • Thorsen S.B.
        • Ekman D.
        • Eriksson A.
        • Rennel Dickens E.
        • Ohlsson S.
        • Edfeldt G.
        • Andersson A.C.
        • Lindstedt P.
        • Stenvang J.
        • Gullberg M.
        • Fredriksson S.
        Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability.
        PLoS One. 2014; 9e95192
        • Beck F.
        • Geiger J.
        • Gambaryan S.
        • Solari F.A.
        • Dell'Aica M.
        • Loroch S.
        • Mattheij N.J.
        • Mindukshev I.
        • Potz O.
        • Jurk K.
        • Burkhart J.M.
        • Fufezan C.
        • Heemskerk J.W.
        • Walter U.
        • Zahedi R.P.
        • Sickmann A.
        Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition.
        Blood. 2017; 129: e1-e12
        • Burkhart J.M.
        • Gambaryan S.
        • Watson S.P.
        • Jurk K.
        • Walter U.
        • Sickmann A.
        • Heemskerk J.W.
        • Zahedi R.P.
        What can proteomics tell us about platelets?.
        Circ. Res. 2014; 114: 1204-1219
        • Maynard D.M.
        • Heijnen H.F.
        • Horne M.K.
        • White J.G.
        • Gahl W.A.
        Proteomic analysis of platelet alpha-granules using mass spectrometry.
        J. Thromb. Haemost. 2007; 5: 1945
        • Pagel O.
        • Walter E.
        • Jurk K.
        • Zahedi R.P.
        Taking the stock of granule cargo: platelet releasate proteomics.
        Platelets. 2017; 28: 119-128
        • Solari F.A.
        • Mattheij N.J.
        • Burkhart J.M.
        • Swieringa F.
        • Collins P.W.
        • Cosemans J.M.
        • Sickmann A.
        • Heemskerk J.W.
        • Zahedi R.P.
        Combined quantification of the global proteome, phosphoproteome, and proteolytic cleavage to characterize altered platelet functions in the human scott syndrome.
        Mol. Cell. Proteomics. 2016; 15: 3154-3169
        • Zimman A.
        • Titz B.
        • Komisopoulou E.
        • Biswas S.
        • Graeber T.G.
        • Podrez E.A.
        Phosphoproteomic analysis of platelets activated by pro-thrombotic oxidized phospholipids and thrombin.
        PLoS One. 2014; 9e84488
        • Coppinger J.A.
        • Maguire P.B.
        Insights into the platelet releasate.
        Curr. Pharm. Des. 2007; 13: 2640-2646
        • Chimen M.
        • Evryviadou A.
        • Box C.L.
        • Harrison M.J.
        • Hazeldine J.
        • Dib L.H.
        • Kuravi S.J.
        • Payne H.
        • Price J.M.J.
        • Kavanagh D.
        • Iqbal A.J.
        • Lax S.
        • Kalia N.
        • Brill A.
        • Thomas S.G.
        • Belli A.
        • Crombie N.
        • Adams R.A.
        • Evans S.A.
        • Deckmyn H.
        • Lord J.M.
        • Harrison P.
        • Watson S.P.
        • Nash G.B.
        • Rainger G.E.
        Appropriation of GPIbalpha from platelet-derived extracellular vesicles supports monocyte recruitment in systemic inflammation.
        Haematologica. 2020; 105: 1248-1261
        • Montague S.J.
        • Andrews R.K.
        • Gardiner E.E.
        Mechanisms of receptor shedding in platelets.
        Blood. 2018; 132: 2535-2545
        • Aloui C.
        • Prigent A.
        • Sut C.
        • Tariket S.
        • Hamzeh-Cognasse H.
        • Pozzetto B.
        • Richard Y.
        • Cognasse F.
        • Laradi S.
        • Garraud O.
        The signaling role of CD40 ligand in platelet biology and in platelet component transfusion.
        Int. J. Mol. Sci. 2014; 15: 22342-22364
        • Todorova D.
        • Simoncini S.
        • Lacroix R.
        • Sabatier F.
        • Dignat-George F.
        Extracellular vesicles in angiogenesis.
        Circ. Res. 2017; 120: 1658-1673
        • Barrachina M.N.
        • Calderon-Cruz B.
        • Fernandez-Rocca L.
        • Garcia A.
        Application of extracellular vesicles proteomics to cardiovascular disease: guidelines, data analysis, and future perspectives.
        Proteomics. 2019; 19e1800247
        • Blair P.
        • Flaumenhaft R.
        Platelet alpha-granules: basic biology and clinical correlates.
        Blood Rev. 2009; 23: 177-189
        • Chatterjee M.
        • Gawaz M.
        Platelet-derived CXCL12 (SDF-1alpha): basic mechanisms and clinical implications.
        J. Thromb. Haemost. 2013; 11: 1954-1967
        • Cheung K.L.
        • Zakai N.A.
        • Folsom A.R.
        • Kurella Tamura M.
        • Peralta C.A.
        • Judd S.E.
        • Callas P.W.
        • Cushman M.
        Measures of kidney disease and the risk of venous thromboembolism in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study.
        Am. J. Kidney Dis. 2017; 70: 182-190
        • Panova-Noeva M.
        • Wagner B.
        • Nagler M.
        • Koeck T.
        • Ten Cate V.
        • Eggebrecht L.
        • Prochaska J.H.
        • Meyer I.
        • Gerdes C.
        • Spronk H.M.
        • Lackner K.J.
        • Ten Cate H.
        • Leineweber K.
        • Heitmeier S.
        • Konstantinides S.
        • Wild P.S.
        Variation of platelet function in clinical phenotypes of acute venous thromboembolism - results from the GMP-VTE project.
        J. Thromb. Haemost. 2022; 20: 705-715
        • Baidildinova G.
        • Nagy M.
        • Jurk K.
        • Wild P.S.
        • Ten Cate H.
        • van der Meijden P.E.J.
        Soluble platelet release factors as biomarkers for cardiovascular disease.
        Front Cardiovasc Med. 2021; 8684920
        • Becattini C.
        • Cohen A.T.
        • Agnelli G.
        • Howard L.
        • Castejon B.
        • Trujillo-Santos J.
        • Monreal M.
        • Perrier A.
        • Yusen R.D.
        • Jimenez D.
        Risk stratification of patients with acute symptomatic pulmonary embolism based on presence or absence of lower extremity DVT: systematic review and meta-analysis.
        Chest. 2016; 149: 192-200
        • Schellong S.M.
        • Goldhaber S.Z.
        • Weitz J.I.
        • Ageno W.
        • Bounameaux H.
        • Turpie A.G.G.
        • Angchaisuksiri P.
        • Haas S.
        • Goto S.
        • Zaghdoun A.
        • Farjat A.
        • Nielsen J.D.
        • Kayani G.
        • Mantovani L.G.
        • Prandoni P.
        • Kakkar A.K.
        Isolated distal deep vein thrombosis: perspectives from the GARFIELD-VTE registry.
        Thromb. Haemost. 2019; 119: 1675-1685
        • Ten Cate V.
        • Eggebrecht L.
        • Schulz A.
        • Panova-Noeva M.
        • Lenz M.
        • Koeck T.
        • Rapp S.
        • Arnold N.
        • Lackner K.J.
        • Konstantinides S.
        • Espinola-Klein C.
        • Munzel T.
        • Prochaska J.H.
        • Wild P.S.
        Isolated pulmonary embolism is associated with a high risk of arterial thrombotic disease: results from the VTEval study.
        Chest. 2020; 158: 341-349
        • Makhoul S.
        • Trabold K.
        • Gambaryan S.
        • Tenzer S.
        • Pillitteri D.
        • Walter U.
        • Jurk K.
        cAMP- and cGMP-elevating agents inhibit GPIbalpha-mediated aggregation but not GPIbalpha-stimulated syk activation in human platelets.
        Cell Commun Signal. 2019; 17: 122
        • Senis Y.A.
        • Mazharian A.
        • Mori J.
        Src family kinases: at the forefront of platelet activation.
        Blood. 2014; 124: 2013-2024
        • Smith H.W.
        • Marshall C.J.
        Regulation of cell signalling by uPAR.
        Nat Rev Mol Cell Biol. 2010; 11: 23-36
        • Mondino A.
        • Blasi F.
        uPA and uPAR in fibrinolysis, immunity and pathology.
        Trends Immunol. 2004; 25: 450-455
        • Humphries J.
        • Gossage J.A.
        • Modarai B.
        • Burnand K.G.
        • Sisson T.H.
        • Murdoch C.
        • Smith A.
        Monocyte urokinase-type plasminogen activator up-regulation reduces thrombus size in a model of venous thrombosis.
        J. Vasc. Surg. 2009; 50: 1127-1134
        • Durrant T.N.
        • Hutchinson J.L.
        • Heesom K.J.
        • Anderson K.E.
        • Stephens L.R.
        • Hawkins P.T.
        • Marshall A.J.
        • Moore S.F.
        • Hers I.
        In-depth PtdIns(3,4,5)P3 signalosome analysis identifies DAPP1 as a negative regulator of GPVI-driven platelet function.
        Blood Adv. 2017; 1: 918-932
        • Moroi A.J.
        • Zwifelhofer N.M.
        • Riese M.J.
        • Newman D.K.
        • Newman P.J.
        Diacylglycerol kinase zeta is a negative regulator of GPVI-mediated platelet activation.
        Blood Adv. 2019; 3: 1154-1166
        • Tang M.Y.Xiaopeng
        • Duan Zilei
        • Liao Zhiyi
        • Liu Lei
        • Cheng Ruomei
        • Fang Mingqian
        • Wang Gan
        • Liu Hongqi
        • Xu Jingwen
        • Kamau Peter M.
        • Zhang Zhiye
        • Yang Lian
        • Zhao Xudong
        • Peng Xiaozhong
        • Lai Ren
        Transferrin receptor is another receptor for SARS-CoV-2 entry, bioRxiv.
        2020
        • Campbell R.A.
        • Boilard E.
        • Rondina M.T.
        Is there a role for the ACE2 receptor in SARS-CoV-2 interactions with platelets?.
        J. Thromb. Haemost. 2021; 19: 46-50
        • Talbot H.
        • Saada S.
        • Naves T.
        • Gallet P.F.
        • Fauchais A.L.
        • Jauberteau M.O.
        Regulatory roles of sortilin and SorLA in immune-related processes.
        Front. Pharmacol. 2018; 9: 1507
        • Canuel M.
        • Korkidakis A.
        • Konnyu K.
        • Morales C.R.
        Sortilin mediates the lysosomal targeting of cathepsins D and H.
        Biochem. Biophys. Res. Commun. 2008; 373: 292-297
        • Yadati T.
        • Houben T.
        • Bitorina A.
        • Shiri-Sverdlov R.
        The ins and outs of cathepsins: physiological function and role in disease management.
        Cells. 2020; 9
        • Jurk K.
        Platelet granules - secretory and secretive.
        Hamostaseologie. 2017; 37: 208-210
        • Horn M.
        • Bertling A.
        • Brodde M.F.
        • Muller A.
        • Roth J.
        • Van Aken H.
        • Jurk K.
        • Heilmann C.
        • Peters G.
        • Kehrel B.E.
        Human neutrophil alpha-defensins induce formation of fibrinogen and thrombospondin-1 amyloid-like structures and activate platelets via glycoprotein IIb/IIIa.
        J. Thromb. Haemost. 2012; 10: 647-661
        • Gleissner C.A.
        • von Hundelshausen P.
        • Ley K.
        Platelet chemokines in vascular disease.
        Arterioscler. Thromb. Vasc. Biol. 2008; 28: 1920-1927
        • Burzynski L.C.
        • Humphry M.
        • Pyrillou K.
        • Wiggins K.A.
        • Chan J.N.E.
        • Figg N.
        • Kitt L.L.
        • Summers C.
        • Tatham K.C.
        • Martin P.B.
        • Bennett M.R.
        • Clarke M.C.H.
        The coagulation and immune systems are directly linked through the activation of interleukin-1alpha by thrombin.
        Immunity. 2019; 50: 1033-1042 e6
        • Dayal S.
        • Wilson K.M.
        • Motto D.G.
        • Miller Jr., F.J.
        • Chauhan A.K.
        • Lentz S.R.
        Hydrogen peroxide promotes aging-related platelet hyperactivation and thrombosis.
        Circulation. 2013; 127: 1308-1316
        • Marchesi C.
        • Dentali F.
        • Nicolini E.
        • Maresca A.M.
        • Tayebjee M.H.
        • Franz M.
        • Guasti L.
        • Venco A.
        • Schiffrin E.L.
        • Lip G.Y.
        • Grandi A.M.
        Plasma levels of matrix metalloproteinases and their inhibitors in hypertension: a systematic review and meta-analysis.
        J. Hypertens. 2012; 30: 3-16
        • Tan J.
        • Hua Q.
        • Xing X.
        • Wen J.
        • Liu R.
        • Yang Z.
        Impact of the metalloproteinase-9/tissue inhibitor of metalloproteinase-1 system on large arterial stiffness in patients with essential hypertension.
        Hypertens. Res. 2007; 30: 959-963
        • Ferroni P.
        • Martini F.
        • Riondino S.
        • La Farina F.
        • Magnapera A.
        • Ciatti F.
        • Guadagni F.
        Soluble P-selectin as a marker of in vivo platelet activation.
        Clin. Chim. Acta. 2009; 399: 88-91
        • Ferroni P.
        • Riondino S.
        • Vazzana N.
        • Santoro N.
        • Guadagni F.
        • Davi G.
        Biomarkers of platelet activation in acute coronary syndromes.
        Thromb. Haemost. 2012; 108: 1109-1123
        • Schaefer J.K.
        • Jacobs B.
        • Wakefield T.W.
        • Sood S.L.
        New biomarkers and imaging approaches for the diagnosis of deep venous thrombosis.
        Curr. Opin. Hematol. 2017; 24: 274-281
        • Blann A.D.
        • Noteboom W.M.
        • Rosendaal F.R.
        Increased soluble P-selectin levels following deep venous thrombosis: cause or effect?.
        Br. J. Haematol. 2000; 108: 191-193
        • Ben-Baruch A.
        • Xu L.
        • Young P.R.
        • Bengali K.
        • Oppenheim J.J.
        • Wang J.M.
        Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors. C-C CKR1, a receptor for macrophage inflammatory protein-1 alpha/Rantes, is also a functional receptor for MCP3.
        J. Biol. Chem. 1995; 270: 22123-22128
        • Labelle M.
        • Begum S.
        • Hynes R.O.
        Platelets guide the formation of early metastatic niches.
        Proc. Natl. Acad. Sci. U. S. A. 2014; 111: E3053-E3061
        • Power C.A.
        • Furness R.B.
        • Brawand C.
        • Wells T.N.
        Cloning of a full-length cDNA encoding the neutrophil-activating peptide ENA-78 from human platelets.
        Gene. 1994; 151: 333-334
        • Davies M.J.
        • Hawkins C.L.
        The role of myeloperoxidase in biomolecule modificationChronic Inflammation, and Disease.
        Antioxid. Redox Signal. 2020; 32: 957-981
        • Krotz F.
        • Sohn H.Y.
        • Pohl U.
        Reactive oxygen species: players in the platelet game.
        Arterioscler. Thromb. Vasc. Biol. 2004; 24: 1988-1996
        • Volf I.
        • Bielek E.
        • Moeslinger T.
        • Koller F.
        • Koller E.
        Modification of protein moiety of human low density lipoprotein by hypochlorite generates strong platelet agonist.
        Arterioscler. Thromb. Vasc. Biol. 2000; 20: 2011-2018
        • Lotvall J.
        • Hill A.F.
        • Hochberg F.
        • Buzas E.I.
        • Di Vizio D.
        • Gardiner C.
        • Gho Y.S.
        • Kurochkin I.V.
        • Mathivanan S.
        • Quesenberry P.
        • Sahoo S.
        • Tahara H.
        • Wauben M.H.
        • Witwer K.W.
        • Thery C.
        Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles.
        J Extracell Vesicles. 2014; 3: 26913
        • Campello E.
        • Spiezia L.
        • Radu C.M.
        • Bulato C.
        • Castelli M.
        • Gavasso S.
        • Simioni P.
        Endothelial, platelet, and tissue factor-bearing microparticles in cancer patients with and without venous thromboembolism.
        Thromb. Res. 2011; 127: 473-477
        • Tesselaar M.E.
        • Romijn F.P.
        • van der Linden I.K.
        • Bertina R.M.
        • Osanto S.
        Microparticle-associated tissue factor activity in cancer patients with and without thrombosis.
        J. Thromb. Haemost. 2009; 7: 1421-1423
        • Chirinos J.A.
        • Heresi G.A.
        • Velasquez H.
        • Jy W.
        • Jimenez J.J.
        • Ahn E.
        • Horstman L.L.
        • Soriano A.O.
        • Zambrano J.P.
        • Ahn Y.S.
        Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism.
        J. Am. Coll. Cardiol. 2005; 45: 1467-1471
        • Ye R.
        • Ye C.
        • Huang Y.
        • Liu L.
        • Wang S.
        Circulating tissue factor positive microparticles in patients with acute recurrent deep venous thrombosis.
        Thromb. Res. 2012; 130: 253-258
        • Chung T.
        • Connor D.
        • Joseph J.
        • Emmett L.
        • Mansberg R.
        • Peters M.
        • Ma D.
        • Kritharides L.
        Platelet activation in acute pulmonary embolism.
        J. Thromb. Haemost. 2007; 5: 918-924
        • Riedl J.
        • Hell L.
        • Kaider A.
        • Koder S.
        • Marosi C.
        • Zielinski C.
        • Panzer S.
        • Pabinger I.
        • Ay C.
        Association of platelet activation markers with cancer-associated venous thromboembolism.
        Platelets. 2016; 27: 80-85