Effects of Tranilast on Inflammasome and Macrophage Phenotype in a Mouse Model of Myocardial Infarction

Acute myocardial infarction (AMI) has been a devastating actuality and accounts for half of cardiovascular emergency department visits. Nucleotide oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome participates in the mediation of myocardial inflammation during AMI. Therefore, this study aimed to reveal the therapeutic function of tranilast, an agent targeting NLRP3, for AMI. AMI mouse model was first established by transient myocardial ischemia. Western blot and quantitative reverse transcription polymerase chain reaction assay were performed to estimate the expression levels of related genes. Flow cytometry was used to analyze the macrophage types, and the therapeutic effects of tranilast were estimated by echocardiographic analysis and Masson's trichrome stain. We demonstrated that AMI induced the activation of NLRP3 inflammasome in the heart tissues of mice with AMI. Tranilast decreased the expression of interleukin-1β and cleaved Caspase-1 in bone marrow-derived macrophages and thus re-educated M1-macrophages toward the M2-phenotype both in vitro and in vivo. Tranilast inhibited the activation in the heart tissues of AMI mice and thus improved cardiac functional recovery in the AMI mouse model. In conclusion, we revealed that tranilast ameliorated myocardial infarction by inhibiting NLRP3 inflammasome and re-educating macrophage phenotype in this study.