Sinapic Acid Attenuated Cardiac Remodeling After Myocardial Infarction by Promoting Macrophage M2 Polarization Through PPARγ Pathway

Background Macrophage polarization is one of the important regulatory mechanisms of ventricular remodeling. Studies have shown sinapic acid (SA) exerts an anti-inflammatory role. However, the effect of SA on macrophage is still unclear. The purpose of the study was to investigate the role of SA in macrophage polarization and ventricular remodeling after myocardial infarction (MI). Methods and results MI model was established by ligating left coronary artery. The rats with MI were treated with SA for 1 week or 4 weeks after MI. The effect of SA on bone marrow-derived macrophages (BMDMs) was also observed in vitro. Cardiac systolic dysfunction was significantly improved after SA treatment. SA reduced MCP-1 and CCR2 expressions and macrophage infiltration. SA decreased inflammatory factors TNF-α, IL-1α and IL-1β levels and increased M2 macrophage marker CD206, Arg-1 and IL-10 levels at 1 week after MI. Myocardial interstitial fibrosis and MMP-2 and MMP-9 levels were declined, and sympathetic nerve marker TH and nerve sprouting marker GAP43 were suppressed after SA treatment at 4 weeks after MI. PPARγ level was notablely upregulated after SA treatment. In vitro, SA also increased expression of PPARγ mRNA in BMDMs and IL-4 induced BMDMs in a concentration-dependent manner. SA enhanced Arg1 and IL-10 expressions in BMDMs and the PPARγ antagonist GW9662 attenuated M2 macrophage markers expressions. Conclusions Our results demonstrated that SA attenuated structural and neural remodeling by promoting macrophage M2 polarization via PPARγ activation after MI.