Dapagliflozin attenuates myocardial fibrosis after myocardial infarction through regulating Lnc-Ang362/miR-200b-3p.

Sodium-Glucose Cotransporter 2 inhibitor (SGLT2i) is cardioprotective in cardiovascular events regardless of diabetes, but the mechanism remains limited. Here, we evaluated the effect of dapagliflozin (DAPA) in myocardial remodeling after myocardial infarction (MI). In this study, 64 Sprague-Dawley rats were randomized into control, sham, MI, and MI + DAPA groups (n = 8 in each group) and had a 4-week treatment. Then the hearts were obtained for further exploration, and primary cardiac fibroblasts (CFs) were induced by transforming growth factor (TGF)-β1 for cellular evaluation. A Luciferase reporter assay was conducted to confirm the candidate target of lnc-Ang362. DAPA treatment significantly improved MI-induced decrease of EF and FS, ventricular dilatation and thinning, myocardial fibrosis, and cell apoptosis in the hearts of MI rats and TGF-β1-treated CFs. In addition, miR-200b-3p was confirmed to be a target of lnc-Ang362. The up-regulated expression of lnc-Ang362 and down-regulated expression of miR-200b-3p were observed in MI hearts and TGF-β1-treated cells, and DAPA could reverse the aberrant expression. DAPA could improve MI-induced cardiac dysfunction and myocardial fibrosis. The anti-fibrosis effect of DAPA related to lnc-Ang362 promotes post-MI cardiac fibrosis by sponging miR-200b-3p.