Leukocyte immunoglobulin-like receptor B2 regulates atherosclerosis progression by modulating macrophage extracellular trap formation in foam macrophages through the PI3K-AKT signaling pathway.

This study aimed to examine the regulatory role of leukocyte immunoglobulin-like receptor B2 (LILRB2) in macrophage extracellular trap (MET) formation in foam macrophages in atherosclerosis (AS). Three datasets were subjected to bioinformatics analysis to identify differentially expressed genes (DEGs). Atherosclerotic lesions from patients with AS were subjected to hematoxylin and eosin and oil red O staining. The levels of lipid regulation-related proteins and inflammatory factors were measured in the lesions. MET formation was induced in oxidized low-density lipoprotein-treated foam macrophages with tumor necrosis factor-alpha (TNF-α). LILRB2 knockdown cells were established to evaluate the role of LILRB2 in MET formation. In a rat AS model, the levels of PI3K/AKT signaling pathway-related molecules and METs were measured in groups classified based on LILRB2 expression. LILRB2 was a key DEG in foam macrophages in AS. The atherosclerotic tissues exhibited increased levels of lipid accumulation and METs and dysregulation of lipid-related and inflammatory factors. Treatment with TNF-α promoted MET formation and LILRB2 expression. Y-P 740 treatment mitigated the LILRB2 knockdown-induced suppression of PI3K/AKT signaling and MET formation. LILRB2 mediated AS pathogenesis by promoting MET formation in foam macrophages via the PI3K/AKT pathway. Targeting LILRB2 and its associated signaling pathway was a potential novel therapeutic strategy for AS.