{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T11:50:57Z","timestamp":1793361057591,"version":"4.5.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,9,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Mineralocorticoid receptor (MR) induces cardiac inflammation cooperatively with nuclear factor\u2010\u03baB and signal transducer and activator of transcription 3 (STAT3); MR blockers exert anti\u2010inflammatory effects. However, the underlying mechanism remains unclear. We investigated the anti\u2010inflammatory effect of esaxerenone, a novel MR blocker, in experimental myocardial infarction (MI) and its underlying mechanisms.<\/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\">Male C57BL\/6J mice subjected to ligation of the left anterior descending artery were randomly assigned to either the vehicle or esaxerenone group. Esaxerenone was provided with a regular chow diet. The mice were euthanized at either 4 or 15\u2009days after MI. Cardiac function, fibrosis, and inflammation were evaluated. Esaxerenone significantly improved cardiac function and attenuated cardiac fibrosis at 15\u2009days after MI independently of its antihypertensive effect. Inflammatory cell infiltration, inflammatory\u2010related gene expression, and elevated serum interleukin\u20106 levels at 4\u2009days after MI were significantly attenuated by esaxerenone. In vitro experiments using mouse macrophage\u2010like cell line RAW264.7 cells demonstrated that esaxerenone\u2010 and spironolactone\u2010attenuated lipopolysaccharide\u2010induced interleukin\u20106 expression without altering the posttranslational modification and nuclear translocation of p65 and STAT3. Immunoprecipitation assays revealed that MR interacted with both p65 and STAT3 and enhanced the p65\u2013STAT3 interaction, leading to a subsequent increase in interleukin\u20106 promoter activity, which was reversed by esaxerenone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Esaxerenone ameliorated postinfarct remodeling in experimental MI through its anti\u2010inflammatory properties exerted by modulating the transcriptional activity of the MR\u2013p65\u2013STAT3 complex. These results suggest that the MR\u2013p65\u2013STAT3 complex can be a novel therapeutic target for treating MI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.123.030941","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T07:17:08Z","timestamp":1725866228000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Mineralocorticoid Receptor Blocker Prevents Mineralocorticoid Receptor\u2013Mediated Inflammation by Modulating Transcriptional Activity of Mineralocorticoid Receptor\u2013p65\u2013Signal Transducer and Activator of Transcription 3 Complex"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5803-5324","authenticated-orcid":false,"given":"Naoto","family":"Kuyama","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Graduate School of Medical Sciences, Kumamoto University Kumamoto 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