Tafolecimab mitigates ox‑LDL‑induced macrophage foam cell formation and inflammation by modulating SR‑A/ABCG1 expression and inhibiting the NF‑κB/MAPK pathways

Macrophage foam‑cell formation, triggered by excessive uptake of oxidized low‑density lipoprotein (ox‑LDL) and subsequent intracellular lipid accumulation, represents a critical pathological event in atherosclerotic plaque initiation that drives localized inflammatory responses. The present study investigated the effects of tafolecimab on ox‑LDL‑induced foam‑cell formation and inflammatory responses in murine macrophages, and further explored the underlying molecular mechanisms. Foam‑cell models were established by exposing RAW264.7 cells to 100 µg/ml ox‑LDL for 24 h. The study groups included a blank control group, a model group, low‑, medium‑ and high‑dose tafolecimab groups (5, 10 and 20 µmol/l, respectively), and a positive control group treated with evolocumab. Intracellular lipid accumulation and cholesterol levels were evaluated using Oil Red O staining and a low‑density lipoprotein‑cholesterol (LDL‑C) assay kit. Western blot analysis was performed to determine the expression of cholesterol metabolism‑related proteins [class A scavenger receptor (SR‑A) and ATP‑binding cassette subfamily G member 1 (ABCG1)] and key components of the nuclear factor‑κB (NF‑κB)/mitogen‑activated protein kinase (MAPK) signaling pathways (NF‑κB p65 and phosphorylated p38). The concentrations of the inflammatory cytokines tumor necrosis factor‑α (TNF‑α) and interleukin‑6 (IL‑6) in the cell supernatant were quantified by enzyme‑linked immunosorbent assay. Compared with the blank control, ox‑LDL treatment markedly increased intracellular lipid‑droplet accumulation and LDL‑C content, confirming the successful establishment of a foam‑cell model. In vitro, compared with the model group, tafolecimab reduced intracellular lipid accumulation and cholesterol content in a dose‑dependent manner (P<0.001). In addition, tafolecimab significantly decreased the expression of the cholesterol influx receptor SR‑A while increasing that of the cholesterol efflux transporter ABCG1 (P<0.001). Furthermore, it effectively inhibited the phosphorylation of NF‑κB p65 and MAPK p38, which was accompanied by reduced secretion of TNF‑α and IL‑6 (P<0.001). The present results indicate that tafolecimab inhibits ox‑LDL‑induced macrophage foam‑cell formation and inflammatory responses, likely by modulating the balance between SR‑A‑mediated cholesterol influx and ABCG1‑mediated cholesterol efflux in favor of cholesterol efflux, and by inhibiting NF‑κB and MAPK pathway activation.