ESC Congress 2026 Abstract · Oct 26, 2026
The sodium–glucose co-transporter 2 inhibitor canagliflozin, attenuates cardiac fibrosis and function in inflammatory dilated cardiomyopathy
By Wang J, Zhang Z, Yang Y
Background: Myocardial fibrosis critically contributes to cardiac dysfunction in inflammatory dilated cardiomyopathy (iDCM). The cardioprotective effects of sodium-glucose cotransporter 2 inhibitors have been demonstrated. However, whether canagliflozin (CANA) can prevent post-inflammatory cardiac fibrosis during the progression of iDCM remains unclear. This study aimed to investigate the effects of CANA on cardiac fibrosis and elucidate the underlying mechanisms. Methods: iDCM was induced in BALB/c mice with myosin heavy chain-α peptides and adjuvant, and CANA (30 mg/kg/day) or saline was orally given. At the end point, cardiac function and fibrosis were measured to investigate the effects of CANA. Human cardiac fibroblasts (HCFs) were cultured to validate the protective effect of CANA in vitro. The following analyses were conducted: proliferation, myofibroblast transformation, and migration assays. Molecular signaling pathways related to the post-inflammatory cardiac fibrosis of iDCM and effects of CANA were evaluated by Western blot, immunofluorescence staining, and protein immunoprecipitation. Results: CANA significantly improved cardiac fibrosis and function in iDCM mice, with no obvious adverse effects on the biochemistry characters. CANA inhibited TGF-β-induced proliferation, myofibroblast transformation, migration, and the synthesis of various extracellular matrix proteins in HCFs. Further analysis revealed that CANA suppressed fibrosis both in vivo and in vitro by inhibiting the expression of FZD8, which interacts with TGF-βRI to regulate the TGF-β/Smad3 pathway. Conclusions: The results indicated that FZD8-mediated TGF-β/Smad3 pathway as a novel downstream key mechanism of TGF-β-induced myofibroblast differentiation and myocardial fibrosis progression in iDCM. CANA attenuated post-inflammatory cardiac fibrosis in iDCM by inhibiting the FZD8-mediated TGF-β/Smad3 pathway.figure 1