{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:48:09Z","timestamp":1790182089831,"version":"4.1.0"},"reference-count":79,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010578","name":"German Cardiac Society","doi-asserted-by":"publisher","award":["DGK03\/2021"],"award-info":[{"award-number":["DGK03\/2021"]}],"id":[{"id":"10.13039\/501100010578","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010578","name":"German Cardiac Society","doi-asserted-by":"publisher","award":["F\/14\/20"],"award-info":[{"award-number":["F\/14\/20"]}],"id":[{"id":"10.13039\/501100010578","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010578","name":"German Cardiac Society","doi-asserted-by":"publisher","award":["WI 5229\/1-1"],"award-info":[{"award-number":["WI 5229\/1-1"]}],"id":[{"id":"10.13039\/501100010578","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005970","name":"German Heart Foundation\/German Foundation of Heart Research","doi-asserted-by":"publisher","award":["DGK03\/2021"],"award-info":[{"award-number":["DGK03\/2021"]}],"id":[{"id":"10.13039\/501100005970","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005970","name":"German Heart Foundation\/German Foundation of Heart Research","doi-asserted-by":"publisher","award":["F\/14\/20"],"award-info":[{"award-number":["F\/14\/20"]}],"id":[{"id":"10.13039\/501100005970","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005970","name":"German Heart Foundation\/German Foundation of Heart Research","doi-asserted-by":"publisher","award":["WI 5229\/1-1"],"award-info":[{"award-number":["WI 5229\/1-1"]}],"id":[{"id":"10.13039\/501100005970","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin","award":["DGK03\/2021"],"award-info":[{"award-number":["DGK03\/2021"]}]},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin","award":["F\/14\/20"],"award-info":[{"award-number":["F\/14\/20"]}]},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin","award":["WI 5229\/1-1"],"award-info":[{"award-number":["WI 5229\/1-1"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DGK03\/2021"],"award-info":[{"award-number":["DGK03\/2021"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["F\/14\/20"],"award-info":[{"award-number":["F\/14\/20"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["WI 5229\/1-1"],"award-info":[{"award-number":["WI 5229\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Atrial myopathy and atrial fibrillation (AF) accompany thrombo-inflammation. This facilitates disease progression and promotes major adverse cardiovascular events (MACEs). Thrombin receptor (protease-activated receptor 1, PAR1) signalling is central in mediating thrombo-inflammation. We hypothesised that PAR1 signalling links coagulation and inflammation through cytotoxic CD8+ T lymphocytes in patients presenting with first-diagnosed AF (FDAF). Methods: A total of 210 patients were studied. We included data and blood samples from patients presenting with FDAF (n = 160), cardiac tissue from patients with paroxysmal AF (n = 32) and 20 controls. Results: During early AF, a pro-inflammatory and cytotoxic subset of T lymphocytes (CD8+) circulated more frequently when compared to patients with chronic cardiovascular disease but without AF, accompanied by elevated plasma levels of CD8+ effector molecules, which corresponded to biomarkers of adverse cardiac remodelling and atrial dysfunction. Activation of tissue factor (TF) and PAR1 was associated with pro-inflammatory and cytotoxic effector functions. PAR1-related CD8+ cell activation was more frequent in FDAF patients that experienced a MACE. Conclusions: In patients with FDAF, the TF-factor Xa-factor IIa-axis contributes to thrombo-inflammation via PAR1 in CD8+ T cells. Intervening in this cascade might be a promising synergistic approach to reducing disease progression and the vascular complications of AF.<\/jats:p>","DOI":"10.3390\/cells12010141","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T03:14:28Z","timestamp":1672370068000},"page":"141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cytotoxic CD8+ T Cells Are Involved in the Thrombo-Inflammatory Response during First-Diagnosed Atrial Fibrillation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8093-8423","authenticated-orcid":false,"given":"Julian","family":"Friebel","sequence":"first","affiliation":[{"name":"Charit\u00e9 Center 11\u2014Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"},{"name":"Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"},{"name":"Department of Cardiac Anesthesiology and Intensive Care Medicine, German Heart Center, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6952-5038","authenticated-orcid":false,"given":"Marco","family":"Witkowski","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center 11\u2014Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"},{"name":"Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Wegner","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center 11\u2014Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Bl\u00f6baum","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center 11\u2014Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Lammel","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center 11\u2014Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp-Alexander","family":"Schencke","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center 11\u2014Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Jakobs","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center 11\u2014Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Puccini","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center 11\u2014Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Rei\u00dfner","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center 11\u2014Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Steffens","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center 11\u2014Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9558-7291","authenticated-orcid":false,"given":"Verena","family":"Moos","sequence":"additional","affiliation":[{"name":"Medical Department I, Gastroenterology, Infectious Diseases and Rheumatology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz-Peter","family":"Schutheiss","sequence":"additional","affiliation":[{"name":"Institute for Cardiac Diagnostics and Therapy (IKDT), 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Landmesser","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center 11\u2014Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"},{"name":"Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1965-973X","authenticated-orcid":false,"given":"Ursula","family":"Rauch","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Center 11\u2014Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/eurheartj\/ehaa612","article-title":"2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC","volume":"42","author":"Hindricks","year":"2020","journal-title":"Eur. 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