{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T22:13:41Z","timestamp":1779315221036,"version":"3.51.4"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,2,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Despite recent advances in pharmacotherapy, heart failure (HF) remains a major cause of hospitalization and death, particularly among aging populations. Sodium\u2013glucose cotransporter 2 inhibitors have reduced hospitalization for HF and cardiovascular death. However, the mechanisms underlying these cardioprotective effects, particularly in the absence of diabetes, remain unclear. Therefore, we aimed to define the cardiac\u2010specific effects of sodium\u2013glucose cotransporter 2 inhibitors and the mechanism by which they improve HF prognoses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">We investigated the cardioprotective properties of empagliflozin in mouse models of HF induced by transverse aortic constriction. Empagliflozin was administered daily for 2\u2009weeks, starting 2\u2009weeks after transverse aortic constriction, and then cardiac function was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Empagliflozin preserved cardiac function and markedly reduced myocardial fibrosis and HF markers. Empagliflozin decreased cardiac C\u2010C chemokine receptor type 2\u2013positive macrophages, suggesting attenuated inflammation. Empagliflozin also reduced C\u2010C motif chemokine ligand 2 expression in cardiac fibroblasts, indicating direct modulation of fibroblast behavior under mechanical stress and inhibited recruitment of proinflammatory macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">We propose a novel antifibrotic mechanism in which empagliflozin acts directly on mechanically stressed cardiac fibroblasts to reduce chemokine signaling and macrophage\u2010mediated inflammation. This mechanosensitive, fibroblast\u2010targeted action might represent a paradigm shift in understanding sodium\u2013glucose cotransporter 2 inhibitor cardioprotection and lead to new therapeutic strategies to mitigate HF progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.043917","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T10:57:46Z","timestamp":1770807466000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Empagliflozin Attenuates Cardiac Fibrosis by Suppressing Fibroblast\u2010Mediated C\u2010C Motif Chemokine Ligand 2 Expression"],"prefix":"10.1161","volume":"15","author":[{"given":"Eri","family":"Nakai","sequence":"first","affiliation":[{"name":"Kansai Medical University","place":["Hirataka, 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