S1PR1 improves Cardiac Repair by Promoting monocyte/ macrophage infiltration and aggregation via ERK Signaling after myocardial infarction

Background This study aimed investigate the impact and mechanism of S1PR1 on monocyte/macrophage function following myocardial Infarction. Methods We performed cells profiling of Circulating, liver, kidney, and cardiac immune cells in mice challenged with AMI, and the monocyte/macrophage landscape of the infarcted heart were quantified via flow cytometry at 0, 5, and 28 days post-MI. Fluorescence microscopy evaluated monocyte/macrophage fluorescence expression in cardiac tissue. Lentiviral vectors (pCMV.DR8 and pMD2.G) were constructed to infect RAW264.7 macrophages, with optimal multiplicity of infection (MOI) determined. Experimental groups included S1PR1-knockdown, S1PR1-overexpression, U0126 (ERK pathway inhibitor)-treated, and blank control groups. Transwell assays assessed cell migration, while RAW264.7-HUVEC co-cultures evaluated adhesion. Results The experimental group exhibited a significantly higher mononuclear/macrophage count in myocardial tissue compared to controls (P < 0.05). In vitro experiments demonstrated that SEW2871 enhanced both adhesion and migration capacities of RAW264.7 macrophages. These effects were significantly attenuated following S1PR1 gene knockdown. Furthermore, U0126 pretreatment substantially diminished SEW2871-mediated promotion of cellular adhesion and migration. Conclusion S1PR1 promotes monocyte/macrophage adhesion and migration via ERK signaling pathway and thus ameliorates post-MI cardiac repair.