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The serotonergic system regulates immune cell functions, yet its contribution to post-MI remodeling is incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we investigated the role of serotonin receptor 7 (5-HT7R) in post-infarction inflammation and outcome after permanent left anterior coronary artery ligation in mice, and complementary analysis of peripheral blood mononuclear cells (PBMCs) obtained from patients with acute MI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three days after MI, 5-HT7R mRNA expression was significantly upregulated in the infarct region compared to remote myocardium and sham operated mice. RNA-sequencing of isolated murine CD11b\n                      <jats:sup>+<\/jats:sup>\n                      cells demonstrated high 5-HT7R expression in cardiac macrophages during the acute phase, which was confirmed by immunohistochemistry. Systemic 5-HT7R-knockout did not affect basal cardiac function but resulted in impaired left ventricular function and enhanced inflammatory signatures 14\u2009days after MI without changes in infarct size. Pharmacological activation of 5-HT7R signaling with the selective agonist LP-211 increased survival after MI, although global systolic function among survivors was not improved. Transcriptomic profiling of cardiac macrophages 3\u2009days after MI revealed bidirectional regulation of inflammatory and metabolic programs depending on 5-HT7R activity, including altered expression of\n                      <jats:italic>Got1<\/jats:italic>\n                      and\n                      <jats:italic>S100A9<\/jats:italic>\n                      . Complementary, in PBMCs from MI patients\n                      <jats:italic>Got1<\/jats:italic>\n                      expression was reduced, while\n                      <jats:italic>S100A9<\/jats:italic>\n                      was increased, and both correlated with 5-HT7R expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data suggest 5-HT7R as a regulator of post-MI immune responses and a potential target to improve repair and survival.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08423-4","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T19:34:16Z","timestamp":1781724856000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serotonin 5-HT7 receptor signaling modulates inflammatory responses and survival after myocardial infarction"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0525-0714","authenticated-orcid":false,"given":"Franziska E.","family":"M\u00fcller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-0103","authenticated-orcid":false,"given":"Frauke S.","family":"Bahr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9586-0202","authenticated-orcid":false,"given":"Sergej","family":"Erschow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Kasten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"Heimerl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Benen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Scherr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1376-7318","authenticated-orcid":false,"given":"Christine S.","family":"Falk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2275-4263","authenticated-orcid":false,"given":"Christian","family":"Bustamante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7253-4821","authenticated-orcid":false,"given":"Igor","family":"Ponomarev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-117X","authenticated-orcid":false,"given":"Johann","family":"Bauersachs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6065-9649","authenticated-orcid":false,"given":"Denise","family":"Hilfiker-Kleiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4360-1511","authenticated-orcid":false,"given":"Thomas","family":"Thum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4570-5130","authenticated-orcid":false,"given":"Evgeni G.","family":"Ponimaskin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5479-2275","authenticated-orcid":false,"given":"Melanie","family":"Ricke-Hoch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"issue":"4","key":"8423_CR1","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1001\/jamacardio.2018.0218","volume":"3","author":"P Chatterjee","year":"2018","unstructured":"Chatterjee P, Joynt Maddox KE. 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All patients were informed and provided a written consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All animal studies were conducted in accordance with German animal protection law and with the European Communities Council Directive 86\/609\/EEC and 2010\/63\/EU for the protection of animals used for experimental purposes under consideration of the ARRIVE guidelines. 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