{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:03:40Z","timestamp":1789715020500,"version":"4.0.1"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Myocardial fibrosis is a pivotal pathological component of the failing heart where the sympatho\u2010\u03b2\u2010adrenergic receptor (\u03b2\u2010AR) signaling is augmented. Intermediate\u2010conductance Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010activated K\n                      <jats:sup>+<\/jats:sup>\n                      channel (K\n                      <jats:sub>Ca<\/jats:sub>\n                      3.1) is expressed in fibroblasts and mediates fibrosis, but the regulation of K\n                      <jats:sub>Ca<\/jats:sub>\n                      3.1 expression by \u03b2\u2010AR activation remains unclear. Used for treatment of skin diseases, dimethyl fumarate (DMF) is recently found to suppress transcription cofactor yes\u2010associated protein (YAP). Here, we examined whether DMF ameliorates myocardial fibrosis induced by \u03b2\u2010AR activation through inhibiting YAP\u2010mediated K\n                      <jats:sub>Ca<\/jats:sub>\n                      3.1 expression in fibroblasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We used 2 mouse models of established cardiac fibrosis induced by administration of isoproterenol (30\u2009mg\/kg per d SC) for 1\u2009week with animals studied 4\u2009weeks afterwards, or transgenic overexpression of \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010AR (\u03b22\u2010TG) exhibiting age\u2010related worsening of cardiac fibrosis. In both models, DMF was administered (50\u2009mg\/kg per d IP) for 4\u2009weeks. The mechanism of DMF in regulating K\n                      <jats:sub>Ca<\/jats:sub>\n                      3.1 expression was studied in cultured adult mouse cardiac fibroblasts exposed to isoproterenol.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Mice subjected to repeated isoproterenol injections developed myocardial inflammation and fibrosis with irreversible cardiac dysfunction. These phenotypes seen in both models were reversed by DMF treatment in\u00a0vivo. Mechanistically, in both in\u00a0vivo models and in cultured fibroblasts, we observed declined YAP phosphorylation and enhanced YAP nuclear localization induced by isoproterenol, changes accompanied by upregulation of K\n                      <jats:sub>Ca<\/jats:sub>\n                      3.1 expression at mRNA and protein levels. These changes were largely abolished by DMF treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      DMF reverses the established myocardial fibrosis following \u03b2\u2010AR activation by inhibiting YAP nuclear localization and resultant K\n                      <jats:sub>Ca<\/jats:sub>\n                      3.1 expression in fibroblasts.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.046565","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T11:08:35Z","timestamp":1773832115000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Dimethyl Fumarate Reverses \u03b2\u2010Adrenoceptor\u2013Mediated Myocardial Fibrosis in Mice by Inhibiting Yes\u2010Associated Protein\u2013Regulated Expression of Intermediate\u2010Conductance Ca\n                    <sup>2+<\/sup>\n                    \u2010Activated K\n                    <sup>+<\/sup>\n                    Channel in Fibroblasts"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3815-5338","authenticated-orcid":false,"given":"Lin\u2010Hong","family":"Wu","sequence":"first","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center","place":["Xi\u2019an, China"]},{"name":"Xi\u2019an Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru\u2010Yue","family":"Bai","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University 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