{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T07:25:26Z","timestamp":1787297126705,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030007"],"award-info":[{"award-number":["82030007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20398"],"award-info":[{"award-number":["U23A20398"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Pathological cardiac hypertrophy precipitates heart failure. Empagliflozin (EMPA), a sodium\u2010glucose cotransporter 2 (SGLT2) inhibitor, confers cardiovascular protection beyond glycaemic control, but the molecular basis of its direct anti\u2010hypertrophic action remains undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Angiotensin II (Ang II)\u2013induced hypertrophy was modelled in AC16 and H9c2 cardiomyocytes, and pressure overload was modelled in mice undergoing transverse aortic constriction (TAC). Outcomes were assessed by cell surface area, marker expression, histology and echocardiography. Mechanistic studies included transcriptomic profiling, integrin subunit analysis, pharmacological integrin blockade with ATN\u2010161, downstream signalling, in silico EMPA\u2013SP1 docking and SP1 knockdown. Blood glucose, body weight and urinary glucose were monitored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>EMPA attenuated Ang II\u2013induced cardiomyocyte hypertrophy in vitro and TAC\u2010induced dysfunction, hypertrophy and interstitial fibrosis in vivo. Transcriptomic analysis revealed enrichment of extracellular matrix\u2010receptor interaction, focal adhesion and cytoskeleton pathways, implicating integrin signalling. TAC up\u2010regulated integrin subunits, which EMPA normalized. ATN\u2010161 abrogated EMPA\u2010mediated suppression of hypertrophic readouts and restored FAK\/Src\/Akt activation, demonstrating functional integrin dependency. Docking predicted a high\u2010affinity EMPA\u2013SP1 interaction; SP1 knockdown reduced basal integrin expression and abolished EMPA\u2010mediated reversal of Ang II\u2013induced ITGA5\/ITGB1 up\u2010regulation, providing functional support.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>EMPA inhibits pathological cardiac hypertrophy by modulating integrin\u2010dependent signal transduction and downstream FAK\/Src\/Akt signalling, potentially through an SP1\u2010associated transcriptional program that influences integrin expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70637","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T07:10:41Z","timestamp":1787296241000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Empagliflozin inhibits cardiac hypertrophy via a mechanism involving integrin signalling"],"prefix":"10.1111","author":[{"given":"Gan","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Southwest Medical University  Luzhou Sichuan China"},{"name":"Central Nervous System Drug Key Laboratory of Sichuan Province, Nucleic Acid Medicine of Luzhou Key Laboratory Southwest Medical University  Luzhou Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roudian","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Southwest Medical University  Luzhou Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxiang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Southwest Medical University  Luzhou Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Southwest Medical University  Luzhou Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyang","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Southwest Medical University  Luzhou Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Southwest Medical University  Luzhou Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Affiliated Hospital, Southwest Medical University  Luzhou Sichuan China"},{"name":"Key Laboratory of Medical 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