{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:01:04Z","timestamp":1793314864528,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","funder":[{"name":"Ministry of research and inovation of Romania","award":["PN-III-P4-ID-PCCF-2016-0172"],"award-info":[{"award-number":["PN-III-P4-ID-PCCF-2016-0172"]}],"id":[{"id":"https:\/\/ror.org\/03padf885","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2020,8,14]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale:<\/jats:title>\n                    <jats:p>The alarmin S100A9 has been identified as a potential therapeutic target in myocardial infarction. Short-term S100A9 blockade during the inflammatory phase post-myocardial infarction inhibits systemic and cardiac inflammation and improves cardiac function long term.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To evaluate the impact of S100A9 blockade on postischemic cardiac repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>\n                      We assessed cardiac function, hematopoietic response, and myeloid phagocyte dynamics in WT (wild type) C57BL\/6 mice with permanent coronary artery ligation, treated with the specific S100A9 blocker ABR-238901 for 7 or 21 days. In contrast to the beneficial effects of short-term therapy, extended S100A9 blockade led to progressive deterioration of cardiac function and left ventricle dilation. The treatment reduced the proliferation of Lin\n                      <jats:sup>\u2212<\/jats:sup>\n                      Sca-1\n                      <jats:sup>+<\/jats:sup>\n                      c-Kit\n                      <jats:sup>+<\/jats:sup>\n                      hematopoietic stem and progenitor cells in the bone marrow and the production of proreparatory CD150\n                      <jats:sup>+<\/jats:sup>\n                      CD48\n                      <jats:sup>\u2212<\/jats:sup>\n                      CCR2\n                      <jats:sup>+<\/jats:sup>\n                      hematopoietic stem cells. Monocyte trafficking from the spleen to the myocardium and subsequent phenotype switching to reparatory Ly6C\n                      <jats:sup>lo<\/jats:sup>\n                      MerTK\n                      <jats:sup>hi<\/jats:sup>\n                      macrophages was also impaired, leading to inefficient efferocytosis, accumulation of apoptotic cardiomyocytes, and a larger myocardial scar. The transcription factor Nur77 (Nr4a1 [nuclear receptor subfamily 4 group A member 1]) mediates the transition from inflammatory Ly6C\n                      <jats:sup>hi<\/jats:sup>\n                      monocytes to reparatory Ly6C\n                      <jats:sup>lo<\/jats:sup>\n                      macrophages. S100A9 upregulated the levels and activity of Nur77 in monocytes and macrophages in vitro and in Ly6C\n                      <jats:sup>hi\/int<\/jats:sup>\n                      monocytes in vivo, and S100A9 blockade antagonized these effects. Finally, the presence of reparatory macrophages in the myocardium was also impaired in S100A9\n                      <jats:sup>\u2212\/<\/jats:sup>\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice with permanent myocardial ischemia, leading to depressed cardiac function long term.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>We show that S100A9 plays an important role in both the inflammatory and the reparatory immune responses to myocardial infarction. Long-term S100A9 blockade negatively impacts cardiac recovery and counterbalances the beneficial effects of short-term therapy. These results define a therapeutic window targeting the inflammatory phase for optimal effects of S100A9 blockade as potential immunomodulatory treatment in acute myocardial infarction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.120.315865","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T05:00:13Z","timestamp":1590037213000},"page":"664-676","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":217,"title":["S100A9 Links Inflammation and Repair in Myocardial Infarction"],"prefix":"10.1161","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3581-9900","authenticated-orcid":true,"given":"Goran","family":"Marinkovi\u0107","sequence":"first","affiliation":[{"name":"From the Department of Clinical Sciences Malm\u00f6, Lund University, Sweden (G.M., I.G., J.N., A.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duco Steven","family":"Koenis","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, the Netherlands (D.S.K., V.d.W., C.J.d.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"de Camp","sequence":"additional","affiliation":[{"name":"DeVos Cardiovascular Research Program, Van Andel Institute, Grand Rapids, MI (L.d.C., N.G., S.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Jablonowski","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Lund University, Sweden (R.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Graber","sequence":"additional","affiliation":[{"name":"DeVos Cardiovascular Research Program, Van Andel Institute, Grand Rapids, MI (L.d.C., N.G., S.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"de Waard","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, the Netherlands (D.S.K., V.d.W., C.J.d.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlie Jacoba","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, the Netherlands (D.S.K., V.d.W., C.J.d.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Goncalves","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Sciences Malm\u00f6, Lund University, Sweden (G.M., I.G., J.N., A.S.)"},{"name":"Department of Cardiology, Skane University Hospital, Sweden (I.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Nilsson","sequence":"additional","affiliation":[{"name":"From the Department of Clinical Sciences Malm\u00f6, Lund University, Sweden 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