{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:42:51Z","timestamp":1790390571980,"version":"4.1.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>The alarmins S100A8 and S100A9 are damage-associated molecular patterns, which play a pivotal role in cardiovascular diseases, inflammation, and viral infections. We aimed to investigate their role in Coxsackievirus B3 (CVB3)\u2013induced myocarditis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>\n              S100A8 and S100A9 mRNA expression was 13.0-fold (\n              <jats:italic>P<\/jats:italic>\n              =0.012) and 5.1-fold (\n              <jats:italic>P<\/jats:italic>\n              =0.038) higher in endomyocardial biopsies from patients with CVB3-positive myocarditis compared with controls, respectively. Elimination of CVB3 led to a downregulation of these alarmins. CVB3-infected mice developed an impaired left ventricular function and displayed an increased left ventricular S100A8 and S100A9 protein expression versus controls. In contrast, CVB3-infected S100A9 knockout mice, which are also a complete knockout for S100A8 on protein level, showed an improved left ventricular function, which was associated with a reduced cardiac inflammatory and oxidative response, and lower CVB3 copy number compared with wild-type CVB3 mice. Exogenous application of S100A8 to S100A9 knockout CVB3 mice induced a severe myocarditis similar to wild-type CVB3 mice. In CVB3-infected HL-1 cells, S100A8 and S100A9 enhanced oxidative stress and CVB3 copy number compared with unstimulated infected cells. In CVB3-infected RAW macrophages, both alarmins increased MIP-2 (macrophage inflammatory protein-2) chemokine expression, which was reduced in CVB3 S100A8 knockdown versus scrambled siRNA CVB3 cells.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>S100A8 and S100A9 aggravate CVB3-induced myocarditis and might serve as therapeutic targets in inflammatory cardiomyopathies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.117.004125","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T01:10:40Z","timestamp":1511226640000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":80,"title":["Pathogenic Role of the Damage-Associated Molecular Patterns S100A8 and S100A9 in Coxsackievirus B3\u2013Induced Myocarditis"],"prefix":"10.1161","volume":"10","author":[{"given":"Irene","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"From the Department of Cardiology and Pneumology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum, Germany (I.M., K.P., K.M., B.P., U.K., S.V.L., C.T., K.S.); Berlin-Brandenburg Center for Regenerative Therapies, Charit\u00e9, University Medicine Berlin, Campus Virchow, Germany (I.M., K.P., K.M., K.S., S.V.L., C.T.); DZHK (German Center for Cardiovascular Research), Partner Site Berlin (I.M., K.P., B.P., S.V.L., C.T.); Department of Immunology, University of M\u00fcnster, Germany (T.V.); Inherited..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vogl","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Pneumology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum, Germany (I.M., K.P., K.M., B.P., U.K., S.V.L., C.T., K.S.); Berlin-Brandenburg Center for Regenerative Therapies, Charit\u00e9, University Medicine Berlin, Campus Virchow, Germany (I.M., K.P., K.M., K.S., S.V.L., C.T.); DZHK (German Center for Cardiovascular Research), Partner Site Berlin (I.M., K.P., B.P., S.V.L., C.T.); Department of Immunology, University of M\u00fcnster, Germany (T.V.); Inherited..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Pappritz","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Pneumology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum, Germany (I.M., K.P., K.M., B.P., U.K., S.V.L., C.T., K.S.); Berlin-Brandenburg Center for Regenerative Therapies, Charit\u00e9, University Medicine Berlin, Campus Virchow, Germany (I.M., K.P., K.M., K.S., S.V.L., C.T.); DZHK (German Center for Cardiovascular Research), Partner Site Berlin (I.M., K.P., B.P., S.V.L., C.T.); Department of Immunology, University of M\u00fcnster, Germany (T.V.); Inherited..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kapka","family":"Miteva","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Pneumology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum, Germany (I.M., K.P., K.M., B.P., U.K., S.V.L., C.T., K.S.); Berlin-Brandenburg Center for Regenerative Therapies, Charit\u00e9, University Medicine Berlin, Campus Virchow, Germany (I.M., K.P., K.M., K.S., S.V.L., C.T.); DZHK (German Center for Cardiovascular Research), Partner Site Berlin (I.M., K.P., B.P., S.V.L., C.T.); Department of Immunology, University of M\u00fcnster, Germany (T.V.); Inherited..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Savvatis","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Pneumology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum, Germany (I.M., K.P., K.M., B.P., U.K., S.V.L., C.T., K.S.); Berlin-Brandenburg Center for Regenerative Therapies, Charit\u00e9, University Medicine Berlin, Campus Virchow, Germany (I.M., K.P., K.M., K.S., S.V.L., C.T.); DZHK (German Center for Cardiovascular Research), Partner Site Berlin (I.M., K.P., B.P., S.V.L., C.T.); Department of Immunology, University of M\u00fcnster, Germany (T.V.); Inherited..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Rohde","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Pneumology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum, Germany (I.M., K.P., K.M., B.P., U.K., S.V.L., C.T., K.S.); Berlin-Brandenburg Center for Regenerative Therapies, Charit\u00e9, University Medicine Berlin, Campus Virchow, Germany (I.M., K.P., K.M., K.S., S.V.L., C.T.); DZHK (German Center for Cardiovascular Research), Partner Site Berlin (I.M., K.P., B.P., S.V.L., C.T.); Department of Immunology, University of M\u00fcnster, Germany (T.V.); Inherited..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Most","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Pneumology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum, Germany (I.M., K.P., K.M., B.P., U.K., S.V.L., C.T., K.S.); Berlin-Brandenburg Center for Regenerative Therapies, Charit\u00e9, University Medicine Berlin, Campus Virchow, Germany (I.M., K.P., K.M., K.S., S.V.L., C.T.); DZHK (German Center for Cardiovascular Research), Partner Site Berlin (I.M., K.P., B.P., S.V.L., C.T.); Department of Immunology, University of M\u00fcnster, Germany (T.V.); Inherited..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Lassner","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Pneumology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum, Germany (I.M., K.P., K.M., B.P., U.K., S.V.L., C.T., K.S.); Berlin-Brandenburg Center for Regenerative Therapies, Charit\u00e9, University Medicine Berlin, Campus Virchow, Germany (I.M., K.P., K.M., K.S., S.V.L., C.T.); DZHK (German Center for Cardiovascular Research), Partner Site Berlin (I.M., K.P., B.P., S.V.L., C.T.); Department of Immunology, University of M\u00fcnster, Germany (T.V.); Inherited..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkert","family":"Pieske","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Pneumology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum, Germany (I.M., K.P., K.M., B.P., U.K., S.V.L., C.T., K.S.); Berlin-Brandenburg Center for Regenerative Therapies, Charit\u00e9, University Medicine Berlin, Campus Virchow, Germany (I.M., K.P., K.M., K.S., S.V.L., C.T.); DZHK (German Center for Cardiovascular Research), Partner Site Berlin (I.M., K.P., B.P., S.V.L., C.T.); Department of Immunology, University of M\u00fcnster, Germany (T.V.); Inherited..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"K\u00fchl","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Pneumology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum, Germany (I.M., K.P., K.M., B.P., U.K., S.V.L., C.T., K.S.); Berlin-Brandenburg Center for Regenerative Therapies, Charit\u00e9, University Medicine Berlin, Campus Virchow, Germany (I.M., K.P., K.M., K.S., S.V.L., C.T.); DZHK (German Center for Cardiovascular Research), Partner Site Berlin (I.M., K.P., B.P., S.V.L., C.T.); Department of Immunology, University of M\u00fcnster, Germany (T.V.); Inherited..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Van Linthout","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology and Pneumology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Campus Virchow Klinikum, Germany (I.M., K.P., K.M., B.P., U.K., S.V.L., C.T., K.S.); Berlin-Brandenburg Center for Regenerative Therapies, Charit\u00e9, University Medicine Berlin, Campus Virchow, Germany (I.M., K.P., K.M., K.S., S.V.L., C.T.); DZHK (German Center for Cardiovascular Research), Partner Site Berlin (I.M., K.P., B.P., S.V.L., C.T.); Department of Immunology, University of M\u00fcnster, Germany (T.V.); 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