{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T14:52:25Z","timestamp":1780757545225,"version":"3.54.1"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFE0103000"],"award-info":[{"award-number":["2018YFE0103000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300435"],"award-info":[{"award-number":["82300435"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The SGLT2 inhibitor empagliflozin (EMPA) has been found to reduce the combined risk of cardiovascular death or hospitalization for heart failure in patients with or without reduced left ventricular ejection fraction, irrespective of diabetes status. The underlying mechanisms remain to be elucidated. Endothelial\u2010to\u2010mesenchymal transition (EndoMT) has been reported to play a pivotal role in the microvascular rarefaction. This study aimed to evaluate the effect of EMPA on angiotensin II (Ang II)\u2010induced left ventricular dysfunction and to explore the underlying mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vivo, C57BL\/6J mice were infused with saline or Ang II (1.5\u2009mg\/kg\/day) and subsequently treated with or without EMPA (10\u2009mg\/kg) for 2\u2009weeks. mRNA sequencing and gene set enrichment analysis (GSEA) indicated that the PI3K\/AKT\/eNOS signalling pathway may mediate the protective effects of empagliflozin in heart failure with preserved ejection fraction (HFpEF). Finally, in\u00a0vitro, PI\u2010103 was used to treat cells, and immunofluorescence, western blotting, qPCR, and other methods were used to verify whether empagliflozin exerts its effects through the PI3K\/AKT\/eNOS pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vivo, the mice treated with Ang II exhibited left ventricular dysfunction, increased microvascular rarefaction, and EndoMT, all of which were attenuated by EMPA treatment. In\u00a0vitro, primary cardiac microvascular endothelial cells (CMECs) exposed to Ang II showed increased EndoMT, which was significantly inhibited by EMPA. EMPA also reversed the downregulation of PI3K\/AKT\/eNOS signalling and nitric oxide (NO) levels. PI\u2010103 abrogated the anti\u2010EndoMT effects of EMPA in CMECs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study suggested that EMPA can protect against Ang II\u2010induced left ventricular dysfunction and microvascular rarefaction by suppressing EndoMT via PI3K\/AKT\/eNOS signalling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jgm.70096","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T09:30:17Z","timestamp":1777541417000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Empagliflozin Ameliorates Angiotensin II\u2010Induced Left Ventricular Diastolic Dysfunction by Suppressing EndoMT via PI3K\/AKT\/eNOS 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