Macrophages play an important role in the progression of acute myocardial infarction (AMI). Studies have shown that sodium-dependent glucose transporter 2 inhibitor (SGLT2i) after AMI could increase the proportion of M2 type/M1 macrophages and reduces adverse ventricular remodeling (AVR) post AMI. This study aimed to investigate whether SGLT2i-pretreated macrophage transplantation could reduce AVR after AMI and the underlying mechanisms. C57BL/6 mice were used to establish an AMI model by ligating the coronary arteries. Dynamic observation of transplanted bone marrow-derived macrophages (BMDMs) was performed using an in vivo imaging system (IVIS). Cardiac function was assessed using echocardiography. The fibrosis ratio was measured using Masson’s trichrome staining. Cardiomyocyte apoptosis was measured using the TUNEL assay. Macrophage subtypes were measured using flow cytometry. We detected the expression of inflammatory factors in the myocardium and serum using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). IVIS revealed that transplanted SGLT2i-pretreated BMDMs were present in the infarcted myocardium for 7 d. Flow cytometry revealed that SGLT2i-pretreated BMDMs promoted the conversion of native-derived macrophages to the M2-type. SGLT2i-pretreated BMDMs also reduced inflammatory factors (IL-6, TNFα, and IL-1β) in the infarcted myocardium and serum. At 28 d post-AMI, SGLT2i-pretreated BMDMs increased cardiac function and vascular density, but reduced cardiomyocyte hypertrophy. SGLT2i-pretreated BMDMs could reduce cardiomyocyte apoptosis and fibrotic area ratio. In conclusion, transplanted SGLT2i-pretreated BMDMs were present in the infarcted myocardium for 7 d and improved AVR by reducing inflammation and modulating the conversion of native mice-derived macrophages to M2-type macrophages.

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