{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:44:52Z","timestamp":1789062292187,"version":"build-2803163510"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,7,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The immune and inflammatory responses play a considerable role in left ventricular remodeling after myocardial infarction (MI). Binding of AhR (aryl hydrocarbon receptor) to its ligands modulates immune and inflammatory responses; however, the effects of AhR in the context of MI are unknown. Therefore, we evaluated the potential association between AhR and MI by treating mice with a nontoxic endogenous AhR ligand, ITE (2\u2010[1\u2019H\u2010indole\u20103\u2019\u2010carbonyl]\u2010thiazole\u20104\u2010carboxylic acid methyl ester). We hypothesized that activation of AhR by ITE in MI mice would boost regulatory T\u2010cell differentiation, modulate macrophage activity, and facilitate infarct healing.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Acute MI was induced in C57BL\/6 mice by ligation of the left anterior descending coronary artery. Then, the mice were randomized to daily intraperitoneal injection of ITE (200\u00a0\u00b5g\/mouse, n=19) or vehicle (n=16) to examine the therapeutic effects of ITE during the postinfarct healing process. Echocardiographic and histopathological analyses revealed that ITE\u2010treated mice exhibited significantly improved systolic function (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and reduced infarct size compared with control mice (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). In addition, we found that ITE increased regulatory T cells in the mediastinal lymph node, spleen, and infarcted myocardium, and shifted the M1\/M2 macrophage balance toward the M2 phenotype in vivo, which plays vital roles in the induction and resolution of inflammation after acute MI. In vitro, ITE expanded the Foxp3\n              <jats:sup>+<\/jats:sup>\n              (forkhead box protein P3\u2010positive) regulatory T cells and tolerogenic dendritic cell populations.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Activation of AhR by a nontoxic endogenous ligand, ITE, improves cardiac function after MI. Post\u2010MI mice treated with ITE have a significantly lower risk of developing advanced left ventricular systolic dysfunction than nontreated mice. Thus, the results imply that ITE has a potential as a stimulator of cardiac repair after MI to prevent heart failure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.020502","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T09:05:32Z","timestamp":1624439132000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Activation of Aryl Hydrocarbon Receptor by ITE Improves Cardiac Function in Mice After Myocardial Infarction"],"prefix":"10.1161","volume":"10","author":[{"given":"Eunhwa","family":"Seong","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute for Intractable Disease College of Medicine The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8386-9275","authenticated-orcid":false,"given":"Jun\u2010Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Pharos Vaccine Inc. Seongnam\u2010si Gyeonggi\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4833-4440","authenticated-orcid":false,"given":"Sungmin","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Cardiology Uijeongbu St. Mary's Hospital College of Medicine The Catholic University of Korea Uijeongbu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun\u2010Hye","family":"Park","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute for Intractable Disease College of Medicine The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunmin","family":"Kim","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute for Intractable Disease College of Medicine The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8430-3903","authenticated-orcid":false,"given":"Chan Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute for Intractable Disease College of Medicine The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunmi","family":"Lee","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute for Intractable Disease College of Medicine The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3056-8791","authenticated-orcid":false,"given":"Gyu\u2010Chul","family":"Oh","sequence":"additional","affiliation":[{"name":"Division of Cardiology Seoul St. Mary's Hospital College of Medicine The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Ho","family":"Choo","sequence":"additional","affiliation":[{"name":"Division of Cardiology Seoul St. Mary's Hospital College of Medicine The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung\u2010Hee","family":"Hwang","sequence":"additional","affiliation":[{"name":"Division of Cardiology Seoul St. Mary's Hospital College of Medicine The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology Uijeongbu St. Mary's Hospital College of Medicine The Catholic University of Korea Uijeongbu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5017-5421","authenticated-orcid":false,"given":"Sang 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