Effect and mechanism of astragalus polysaccharide on lipid metabolism of macrophages / 西安交通大学学报(医学版)

ABSTRACT

Objective: To explore the effect of astragalus polysaccharide (APS) on oxidized low-density lipoprotein (ox-LDL)-induced lipid metabolism of macrophages and its underlying mechanism. Methods: The small interfering RNA (siRNA) targeting ATP binding cassette transporter A1 (ABCA1) was transfected into RAW 264.7 macrophages. Then the cells were stimulated with various concentrations of APS (20 mg/L, 60 mg/L and 150 mg/L), followed by the incubation with 50 mg/L ox-LDL for 24 h. qRT-PCR and Western blot were used to investigate the expression of ABCA1 mRNA and protein. Oil red O was used to analyze the level of foam cells. Lipid accumulation level was assessed by high performance liquid chromatography. [3H]-cholesterol was used to evaluate cholesterol efflux. Results: APS dose-dependently inhibited ox-LDL-induced formation of macrophage-derived foam cell compared with those in control group (P<0.05). HPLC analysis confirmed that APS attenuated lipid accumulation in a dose-dependent manner based on the decrease in ratio of cholesterol ester (CE)/total cholesterol (TC), concomitant with up-regulation of cholesterol efflux (P<0.05), indicating that APS might inhibit lipid deposition in macrophage by enhancing reverse cholesterol transport. Further more, APS dose-dependently increased ABCA1 mRNA and protein levels (P<0.05). When silencing ABCA1 expression with its specific siRNA, APS-inhibited lipid accumulation was significantly up-regulated, accompanied with the down-regulation of cholesterol efflux (P<0.05). Conclusion: APS may regulate lipid metabolism of macrophages by ABCA1-mediated progress of reverse cholesterol transport. Therefore, this study provides a potential target for the treatment of cardiovascular diseases triggered by vulnerable plaque.