{
    "abstract": "Thrombin-activated platelets can promote fibrinolysis by binding plasminogen in a fibrinogen-dependent manner and enhancing its activation by tissue-type plasminogen activator (t-PA). Whether t-PA also binds to activated platelets and the mechanism for regulation of platelet-dependent fibrinolysis remain unknown.\nDetermine the mechanism of plasminogen and t-PA binding on thrombin-activated platelets and its regulation by activated thrombin-activatable fibrinolysis inhibitor (TAFIa).\nPlasminogen and t-PA binding with or without TAFIa treatment was quantified using flow cytometry. Plasmin generation on platelets was quantified using a plasmin-specific substrate. Mass spectrometry analyses identified fibrinogen as a potential target of TAFIa. Thrombus formation was studied in mice lacking fibrinogen (Fg\nPlasminogen and t-PA bind to platelets activated by thrombin but not by other agonists, including protease-activated receptor agonists (PAR-AP). Plasminogen binds via its kringle domains because \u03b5-aminocaproic acid eliminates binding, whereas t-PA binds via its finger and kringle domains. Plasminogen binding is fibrinogen-dependent because it is abolished on (a) Fg\nThese findings provide novel mechanistic insights into how platelets activated by thrombin at sites of vascular injury can influence fibrinolysis.",
    "authors": [
        {
            "affiliation": "Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.\nDepartments of Medicine and Medical Sciences, McMaster University, Hamilton, ON, Canada.",
            "firstname": "Ran",
            "initials": "R",
            "lastname": "Ni"
        },
        {
            "affiliation": "Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto Platelet Immunobiology Group, Toronto, ON, Canada.",
            "firstname": "Miguel A D",
            "initials": "MAD",
            "lastname": "Neves"
        },
        {
            "affiliation": "Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.",
            "firstname": "Chengliang",
            "initials": "C",
            "lastname": "Wu"
        },
        {
            "affiliation": "Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.",
            "firstname": "Samantha E",
            "initials": "SE",
            "lastname": "Cerroni"
        },
        {
            "affiliation": "Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Research Foundation, Cincinnati, OH, USA.",
            "firstname": "Matthew J",
            "initials": "MJ",
            "lastname": "Flick"
        },
        {
            "affiliation": "Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto Platelet Immunobiology Group, Toronto, ON, Canada.\nCanadian Blood Services Centre for Innovation, Toronto, ON, Canada.\nDepartment of Medicine and Physiology, University of Toronto, Toronto, ON, Canada.",
            "firstname": "Heyu",
            "initials": "H",
            "lastname": "Ni"
        },
        {
            "affiliation": "Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.\nDepartments of Medicine and Medical Sciences, McMaster University, Hamilton, ON, Canada.",
            "firstname": "Jeffrey I",
            "initials": "JI",
            "lastname": "Weitz"
        },
        {
            "affiliation": "Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.\nDepartments of Medicine and Medical Sciences, McMaster University, Hamilton, ON, Canada.",
            "firstname": "Peter L",
            "initials": "PL",
            "lastname": "Gross"
        },
        {
            "affiliation": "Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.\nDepartments of Medicine and Medical Sciences, McMaster University, Hamilton, ON, Canada.",
            "firstname": "Paul Y",
            "initials": "PY",
            "lastname": "Kim"
        }
    ],
    "conclusions": "These findings provide novel mechanistic insights into how platelets activated by thrombin at sites of vascular injury can influence fibrinolysis.",
    "copyrights": "\u00a9 2020 International Society on Thrombosis and Haemostasis.",
    "doi": "10.1111/jth.14950",
    "journal": "Journal of thrombosis and haemostasis : JTH",
    "keywords": [
        "blood platelets",
        "carboxypeptidase B2",
        "fibrinolysis",
        "intravital microscopy",
        "plasminogen"
    ],
    "methods": null,
    "publication_date": "2020-06-09",
    "pubmed_id": "32506822\n3030730\n3088041\n7199524\n22187433\n8663147\n25712989\n3179439\n12855554\n3920216\n3086385\n22974122\n11170397\n2550424\n28640323\n19074424\n8999920\n2129142\n3139714\n7649481\n10930441\n22995523\n25128532\n16824188\n12244306\n15226545\n10674406\n11520817\n19897580\n25806939\n22463102\n23383331\n23584880\n18086864\n18278053\n19408189\n29434246\n22235124\n16091450\n23560673",
    "results": "Plasminogen and t-PA bind to platelets activated by thrombin but not by other agonists, including protease-activated receptor agonists (PAR-AP). Plasminogen binds via its kringle domains because \u03b5-aminocaproic acid eliminates binding, whereas t-PA binds via its finger and kringle domains. Plasminogen binding is fibrinogen-dependent because it is abolished on (a) Fg",
    "title": "Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) attenuates fibrin-dependent plasmin generation on thrombin-activated platelets.",
    "xml": "<Element 'PubmedArticle' at 0x788503734a90>"
}