LAUSR

Graphical abstract Figure. No caption available. HighlightsLAIR‐1 was down‐regulated in macrophage with the stimulation of ox‐LDL.Silencing expression of LAIR‐1 in human macrophages increased cholesterol uptake.LAIR‐1 activated phosphorylation of SHP‐1 and CREB to induce PPAR&ggr;, thus promoting M2 polarization and foam cell formation.Targeting LAIR‐1 may provide a potential therapeutic strategy for atherosclerosis. Abstract Formation of macrophage‐derived foam cells may mark the initial stages of atherosclerosis. We investigated the association between the expression of the leukocyte‐associated immunoglobulin‐like receptor 1 (LAIR‐1) in macrophages and foam cell formation. A foam cell model was established by incubating THP‐1‐derived macrophages and bone marrow macrophages (BMMs) with oxidized low‐density lipoprotein (ox‐LDL). The role of LAIR‐1 in foam cell formation was evaluated via Oil Red O staining and Dil‐ox‐LDL fluorescence intensities. Peroxisome proliferator‐activated receptor gamma (PPAR&ggr;), cholesterol metabolism‐related genes, and the role of LAIR‐1 in activating classically activated (M1) and alternatively activated (M2) macrophages were evaluated by qPCR. Additionally, activation of protein‐tyrosine phosphatase‐1 (SHP‐1) and cAMP‐response element binding protein (CREB) were detected by western blotting. Results indicated that silencing LAIR‐1 in macrophages modulated the SHP‐1/CREB/PPAR&ggr; pathway, thereby promoting M2 macrophage polarization and increasing foam cell formation. Therefore, Inhibition of LAIR‐1 in macrophages may promote foam cell formation and atherosclerosis.