The SGLT2 inhibitor dapagliflozin alleviates ventricular remodeling and apoptosis after myocardial infarction by inhibiting the TGF-β1 and MAPK pathways

Heart failure and ventricular remodeling are the major cardiac injuries after myocardial infarction (MI). Sodium‒glucose cotransporter 2 (SGLT2) inhibitors have been shown to be effective at alleviating heart failure and improving patient outcomes and quality of life. However, whether SGLT2 has the same effect on myocardial infarction is unclear. The aim of this study was to elucidate the efficacy and underlying mechanisms of dapagliflozin on the outcome of myocardial infarction. A porcine model of myocardial infarction was established via percutaneous coronary intervention with a balloon-dilated catheter and treated with dapagliflozin (DPG), an SGLT2 inhibitor, for 8 weeks. The biochemical indices of pig blood were determined. M-mode echocardiography was performed to determine cardiac structure and function. HE staining, Masson staining and TUNEL were used to detect myocardial fibrosis and apoptosis. The expression of target proteins in signal transduction pathways was determined by Western blotting. DPG treatment ameliorated myocardial hypertrophy and fibrosis and increased collagen synthesis and apoptosis induced by myocardial infarction in pigs. Moreover, DPG inhibited the activation of the TGF-β1 and MAPK signaling pathways. DPG can effectively reduce ventricular remodeling and myocardial cell apoptosis after myocardial infarction. DPG inhibits the TGF-β1 and MAPK pathways.