{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T05:26:32Z","timestamp":1793942792221,"version":"4.8.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"38","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100010447","name":"German Centre for Cardiovascular Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017268","name":"Berlin Institute of Health","doi-asserted-by":"publisher","award":["PRIN 2017, Protocol 2017WJBKKW_001"],"award-info":[{"award-number":["PRIN 2017, Protocol 2017WJBKKW_001"]}],"id":[{"id":"10.13039\/501100017268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>In one-third of patients with acute coronary syndrome (ACS), thrombosis occurs despite an intact fibrous cap (IFC) (IFC\u2013ACS, \u2018plaque erosion\u2019). Recent studies emphasize neutrophils as the immediate inflammatory response in this pathology, but their exact molecular activation patterns are still poorly understood and may represent future therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Thirty-two patients with IFC\u2013ACS and matched patients with ACS with ruptured fibrous cap (RFC) (RFC\u2013ACS) from the OPTICO\u2013ACS study were included, and blood samples were collected from the local site of the culprit lesion and the systemic circulation. Neutrophil surface marker expression was quantified by flow cytometry. Neutrophil cytotoxicity towards endothelial cells was examined in an ex vivo co-culture assay. Secretion of active matrix metalloproteinase 9 (MMP9) by neutrophils was evaluated using zymography in supernatants and in plasma samples. Optical coherence tomography (OCT)\u2013embedded thrombi were used for immunofluorescence analysis. Toll-like receptor 2 (TLR2) expression was higher on neutrophils from IFC\u2013ACS than RFC\u2013ACS patients. TLR2 stimulation increased the release of active MMP9 from local IFC\u2013ACS\u2013derived neutrophils, which also aggravated endothelial cell death independently of TLR2. Thrombi of IFC\u2013ACS patients exhibited more hyaluronidase 2 with concomitant increase in local plasma levels of the TLR2 ligand: hyaluronic acid.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The current study provides first in-human evidence for distinct TLR2-mediated neutrophil activation in IFC\u2013ACS, presumably triggered by elevated soluble hyaluronic acid. Together with disturbed flow conditions, neutrophil-released MMP9 might be promoting endothelial cell loss\u2013triggered thrombosis and therefore providing a potential future target for a phenotype-specific secondary therapeutic approach in IFC\u2013ACS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehad379","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T19:47:54Z","timestamp":1685044074000},"page":"3892-3907","source":"Crossref","is-referenced-by-count":45,"title":["Toll-like receptor 2, hyaluronan, and neutrophils play a key role in plaque erosion: the OPTICO\u2013ACS study"],"prefix":"10.1093","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4741-924X","authenticated-orcid":false,"given":"Denitsa","family":"Meteva","sequence":"first","affiliation":[{"name":"Deutsches Herzzentrum der Charit\u00e9, Department of Cardiology, Angiology and Intensive Care Medicine , Hindenburgdamm 30, Berlin 12203 , Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , Charit\u00e9platz 1, Berlin 10117 , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research) partner Site Berlin , Berlin 12203 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3632-5934","authenticated-orcid":false,"given":"Ramona","family":"Vinci","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Largo Francesco Vito 1, Rome 00168, Italy"},{"name":"Department of Cardiovascular Sciences, IRCCS Fondazione Policlinico Universitario A. Gemelli, Largo Francesco Vito 1, Rome 00168, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4892-6809","authenticated-orcid":false,"given":"Claudio","family":"Seppelt","sequence":"additional","affiliation":[{"name":"Deutsches Herzzentrum der Charit\u00e9, Department of Cardiology, Angiology and Intensive Care Medicine , Hindenburgdamm 30, Berlin 12203 , Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , Charit\u00e9platz 1, Berlin 10117 , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research) partner Site Berlin , Berlin 12203 , Germany"},{"name":"Department of Cardiology and Angiology, Goethe University, Theodor-Stern-Kai 7, Frankfurt am Main 60598, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef S","family":"Abdelwahed","sequence":"additional","affiliation":[{"name":"Deutsches Herzzentrum der Charit\u00e9, Department of Cardiology, Angiology and Intensive Care Medicine , Hindenburgdamm 30, Berlin 12203 , Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , Charit\u00e9platz 1, Berlin 10117 , Germany"},{"name":"DZHK (German Centre for Cardiovascular Research) partner Site Berlin , Berlin 12203 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Pedicino","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Largo Francesco Vito 1, Rome 00168, Italy"},{"name":"Department of Cardiovascular Sciences, IRCCS Fondazione Policlinico Universitario A. 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