{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:19:19Z","timestamp":1785449959188,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stein Erik Hagens Foundation for Clinical Heart Research","award":["2022012"],"award-info":[{"award-number":["2022012"]}]},{"name":"Stein Erik Hagens Foundation for Clinical Heart Research","award":["43600"],"award-info":[{"award-number":["43600"]}]},{"name":"Blix Foundation for the Promotion of Medical Research","award":["2022012"],"award-info":[{"award-number":["2022012"]}]},{"name":"Blix Foundation for the Promotion of Medical Research","award":["43600"],"award-info":[{"award-number":["43600"]}]},{"name":"Ada og Hagbart Waages Humanit\u00e6re og Veldedige Stiftelse","award":["2022012"],"award-info":[{"award-number":["2022012"]}]},{"name":"Ada og Hagbart Waages Humanit\u00e6re og Veldedige Stiftelse","award":["43600"],"award-info":[{"award-number":["43600"]}]},{"name":"South-Eastern Norway Regional Health Authority","award":["2022012"],"award-info":[{"award-number":["2022012"]}]},{"name":"South-Eastern Norway Regional Health Authority","award":["43600"],"award-info":[{"award-number":["43600"]}]},{"name":"Marie Stenbergs Legat","award":["2022012"],"award-info":[{"award-number":["2022012"]}]},{"name":"Marie Stenbergs Legat","award":["43600"],"award-info":[{"award-number":["43600"]}]},{"name":"National Health Association","award":["2022012"],"award-info":[{"award-number":["2022012"]}]},{"name":"National Health Association","award":["43600"],"award-info":[{"award-number":["43600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammation contributes to myocardial injury in ST-elevation myocardial infarction (STEMI). Interleukin-6 receptor (IL-6R) inhibition has been shown to mitigate myocardial injury and reduce levels of the prothrombotic and inflammatory mediator, neutrophil extracellular traps (NETs). The enzyme peptidylarginine deiminase 4 (PAD4) is central in NET formation. We hypothesized that PAD4 links IL-6R activation and NET formation. Methods: We conducted thrombus aspiration and peripheral blood sampling in 33 STEMI patients. In thrombi and leukocytes, we quantified the mRNA of IL-6, IL-6R, and PAD4. In peripheral blood, the protein levels of IL-6, IL-6R, PAD4, dsDNA, H3Cit, MPO-DNA, and troponin T were quantified. Results: In thrombi and circulating leukocytes, PAD4 mRNA was associated with IL-6R mRNA (thrombi: \u03b2 = 0.34, 95% CI [0.16\u20130.53], p = 0.001, circulating leukocytes: \u03b2 = 0.92, 95% CI [0.07\u20131.77], p = 0.036). There were no correlations between PAD4 and IL-6 in thrombi and leukocytes. The protein levels of IL-6R were associated with the NET marker H3Cit (rs = 0.40, p = 0.02). In thrombi, PAD4 mRNA was associated with high levels of troponin T (\u03b2 = 1.15 95% CI [0.27\u20132.04], p = 0.013). Conclusion: We demonstrate an association between PAD4, IL-6R, and troponin release in STEMI patients. Our findings indicate a PAD4-mediated connection between IL-6R and NET formation and highlight PAD4 as a potential treatment target for mitigating inflammation and myocardial injury in STEMI.<\/jats:p>","DOI":"10.3390\/ijms26115348","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T11:40:32Z","timestamp":1748864432000},"page":"5348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["IL-6R Signaling Is Associated with PAD4 and Neutrophil Extracellular Trap Formation in Patients with STEMI"],"prefix":"10.3390","volume":"26","author":[{"given":"Kristine M\u00f8rk","family":"Kindberg","sequence":"first","affiliation":[{"name":"Oslo Center for Clinical Heart Research, Department of Cardiology Ullevaal, Oslo University Hospital, 0450 Oslo, Norway"},{"name":"Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9680-9688","authenticated-orcid":false,"given":"Jostein","family":"Nordeng","sequence":"additional","affiliation":[{"name":"Oslo Center for Clinical Heart Research, Department of Cardiology Ullevaal, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam Sj\u00e5stad","family":"Langseth","sequence":"additional","affiliation":[{"name":"Department of Cardiology Rikshospitalet, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2517-6382","authenticated-orcid":false,"given":"Hossein","family":"Schandiz","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, 0450 Oslo, Norway"},{"name":"Department of Oncology, Akershus University Hospital, 1478 L\u00f8renskog, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borghild","family":"Roald","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, 0450 Oslo, Norway"},{"name":"Department of Pathology, Oslo University Hospital Ullevaal, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svein","family":"Solheim","sequence":"additional","affiliation":[{"name":"Oslo Center for Clinical Heart Research, Department of Cardiology Ullevaal, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingebj\u00f8rg","family":"Seljeflot","sequence":"additional","affiliation":[{"name":"Oslo Center for Clinical Heart Research, Department of Cardiology Ullevaal, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8869-8153","authenticated-orcid":false,"given":"Mathis Korseberg","family":"Stokke","sequence":"additional","affiliation":[{"name":"Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragnhild","family":"Helseth","sequence":"additional","affiliation":[{"name":"Oslo Center for Clinical Heart Research, Department of Cardiology Ullevaal, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e001869","DOI":"10.1136\/openhrt-2021-001869","article-title":"High levels of interleukin-6 are associated with final infarct size and adverse clinical events in patients with STEMI","volume":"8","author":"Tollefsen","year":"2021","journal-title":"Open Heart"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1007\/s00392-018-1387-z","article-title":"Plasma interleukin 6 levels are associated with cardiac function after ST-elevation myocardial infarction","volume":"108","author":"Groot","year":"2019","journal-title":"Clin. 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