Inhibitory effect of apolipoprotein A-I mimetic peptide D-4F on scavenger receptor A1 in macrophage-derived foam cells

AIM:To investigate the inhibitory effect of apolipoprotein A-I mimetic peptide D-4F on the scavenger receptor A1 (SR-A1) in macrophage-derived foam cells induced by oxidized low-density lipoprotein (ox-LDL). METHODS:RAW264.7 cells were pretreated with different concentrations (12.5, 25 and 50 mg/L) of D-4F or 50 mg/L inactive control peptide scrambled D-4F (sD-4F) for 1 h or endoplasmic reticulum stress (ERS) inhibitor 4-phenylbutyric acid (5 mmol/L) for 30 min, followed by the treatment with 100 mg/L ox-LDL for 12 h. In addition, the cells were pretreated with 50 mg/L D-4F or sD-4F for 1 h, and then stimulated with 2 mg/L tunicamycin (TM; an ERS inducer), for 4 h. The viability of the cells was measured by MTT assay, and the content of intracellular total cholesterol (TC) was measured by a tissue/cell TC assay. The protein and mRNA levels of SR-A1 and glucose-regulated protein 78 (GRP78) were analyzed by Western blotting and quantitative real-time PCR, respectively. The fluorescence intensity of DiI-ox-LDL in the cells was detected by a multifunctional microplate reader. RESULTS:D-4F significantly reduced ox-LDL-induced macrophage injury and intracellular cholesterol accumulation, and attenuated the ox-LDL-induced expression of SRA1 and GRP78 in a dose-dependent manner. Additionally, D-4F significantly inhibited the TM-induced protein expression of SR-A1 and GRP78, and attenuated the uptake of ox-LDL by macrophages. CONCLUSION: D-4F reduces ox-LDL-induced macrophage cholesterol accumulation and injury by inhibiting SR-A1 expression. The mechanism may be related to the inhibition of ERS signaling pathway mediated by GRP78.