Empagliflozin inhibits cardiac hypertrophy via a mechanism involving integrin signalling.

Authors

Gan Qiao, Roudian Lin, Yongxiang Lu, Jianping Wu, Chunyang Ren, Minghua Liu, Chunxiang Zhang

Published in

British journal of pharmacology. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

Pathological cardiac hypertrophy precipitates heart failure. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, confers cardiovascular protection beyond glycaemic control, but the molecular basis of its direct anti-hypertrophic action remains undefined.
Angiotensin II (Ang II)-induced 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-161, downstream signalling, in silico EMPA-SP1 docking and SP1 knockdown. Blood glucose, body weight and urinary glucose were monitored.
EMPA attenuated Ang II-induced cardiomyocyte hypertrophy in vitro and TAC-induced dysfunction, hypertrophy and interstitial fibrosis in vivo. Transcriptomic analysis revealed enrichment of extracellular matrix-receptor interaction, focal adhesion and cytoskeleton pathways, implicating integrin signalling. TAC up-regulated integrin subunits, which EMPA normalized. ATN-161 abrogated EMPA-mediated suppression of hypertrophic readouts and restored FAK/Src/Akt activation, demonstrating functional integrin dependency. Docking predicted a high-affinity EMPA-SP1 interaction; SP1 knockdown reduced basal integrin expression and abolished EMPA-mediated reversal of Ang II-induced ITGA5/ITGB1 up-regulation, providing functional support.
EMPA inhibits pathological cardiac hypertrophy by modulating integrin-dependent signal transduction and downstream FAK/Src/Akt signalling, potentially through an SP1-associated transcriptional program that influences integrin expression.

PMID:
42625452
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

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