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Preclinical models have demonstrated that thrombo-inflammation mediates adverse cardiac remodeling and atherothrombotic events. We have hypothesized that thrombin activity (FIIa) links coagulation with inflammation and cardiac fibrosis\/dysfunction. Surrogate markers of the thrombo-inflammatory response in plasma have not been characterized in FDAF. In this prospective longitudinal study, patients presenting with FDAF (n = 80), and 20 matched controls, were included. FIIa generation and activity in plasma were increased in the patients with early AF compared to the patients with chronic cardiovascular disease without AF (controls; p &lt; 0.0001). This increase was accompanied by elevated biomarkers (ELISA) of platelet and endothelial activation in plasma. Pro-inflammatory peripheral immune cells (TNF-\u03b1+ or IL-6+) that expressed FIIa-activated protease-activated receptor 1 (PAR1) (flow cytometry) circulated more frequently in patients with FDAF compared to the controls (p &lt; 0.0001). FIIa activity correlated with cardiac fibrosis (collagen turnover) and cardiac dysfunction (NT-pro ANP\/NT-pro BNP) surrogate markers. FIIa activity in plasma was higher in patients with FDAF who experienced MACE. Signaling via FIIa might be a presumed link between the coagulation system (tissue factor-FXa\/FIIa-PAR1 axis), inflammation, and pro-fibrotic pathways (thrombo-inflammation) in FDAF.<\/jats:p>","DOI":"10.3390\/ijms25074109","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T10:11:55Z","timestamp":1712571115000},"page":"4109","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Characterization of Biomarkers of Thrombo-Inflammation in Patients with First-Diagnosed Atrial Fibrillation"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8093-8423","authenticated-orcid":false,"given":"Julian","family":"Friebel","sequence":"first","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, 12203 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"},{"name":"Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Wegner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Bl\u00f6baum","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp-Alexander","family":"Schencke","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Jakobs","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Puccini","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Ghanbari","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Lammel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4698-4079","authenticated-orcid":false,"given":"Tharusan","family":"Thevathasan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, 12203 Berlin, Germany"},{"name":"Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10117 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":"Marco","family":"Witkowski","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, 12203 Berlin, Germany"},{"name":"Friede Springer Cardiovascular Prevention Center at Charit\u00e9, 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":"Ulf","family":"Landmesser","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, 12203 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"},{"name":"Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Friede Springer Cardiovascular Prevention Center at Charit\u00e9, 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":"Ursula","family":"Rauch-Kr\u00f6hnert","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, 12203 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany"},{"name":"Friede Springer Cardiovascular Prevention Center at Charit\u00e9, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 12203 Berlin, 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