Transcriptome analysis of Sodium-Glucose Cotransporter-2 Inhibitors in Acute Myocardial Infarction

Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor (SGLT2i), is a new type of oral antidiabetic agent. Here, we examined the effects of DAPA on AMI and investigated the potential mechanisms.Heart tissue specimens were collected from C57BL/6J mice induced by ligation of the left anterior descending coronary artery and treated with DAPA at 1 mg/kg/day dose for 4 weeks after surgery. Echocardiography, histological staining, and RNA sequencing (RNA-seq) of these specimens were performed. The differentially expressed genes of interest were confirmed by qualitative RT-PCR (RT-qPCR) and western blotting (WB). In vitro experiments were performed to evaluate the effect of DAPA on myosin light-chain 4 (Myl4) upregulation and reduction of autophagy following hypoxic treatment. As a result, DAPA could improve cardiac function post MI by upregulating Myl4 and reducing autophagy; this finding suggests that the molecular regulation associated with Myl4 might be an important mechanism of AMI treatment by SGLT2i. Overall design: RNA sequencing (RNA-Seq) of the cardiac tissues from C57BL/6J mice, which was induced by left anterior descending (LAD) coronary artery ligation, treated with DAPA at a dose of 1mg/kg/day for 4 weeks after surgery was conducted. Differentially expressed genes (DEGs) enriched in the mice heart after DAPA treatment were identified at the transcriptome level.