Tanshinone IIA up-regulates the expression of ATP-binding cassette transporter A1 and increases cholesterol efflux in RAW 264.7 macrophage-derived foam cells

Objective: To investigate the effect of tanshinoneⅡA on the formation of foam cells induced by the oxidized low density lipoprotein(ox-LDL) and explore the underlying mechanism.Methods: RAW 264.7 macrophages were incubated with ox-LDL(50 μg/mL) for 48 h to induce foam cells.Cells were treated with tanshinoneⅡA(10–5,10–4,and 10–3 mol/L) for 48 h at the same time.The cellular lipid accumulation was examined by oi1 red staining.The level of cellular total cholesterol(TC),free cholesterol(FC),and cholesteryl ester(CE) were examined by high performance liquid chromatography assays.Cholesterol efflux from macrophages was tested by cholesterol labled by .The mRNA and protein expression of ATP-binding cassette transporter A1(ABCA1) was detected by Real-time PCR and Western blot,respectively.Results: Oil red O staining positive cells were found and macrophages were filled with lipid droplet in the foam cell model group induced by ox-LDL.Compared with the foam cells,tanshinoneⅡA(10–4 and 10–3 mol/L) significantly decreased the amount of oil red O staining positive cells and the levels of lipid droplet of foam cells.The levels of TC,FC,CE,and CE/TC ratio in the foam cell model group were significantly increased compared with the control macrophage group.The levels of TC,FC,CE,and CE/TC ratio were significantly decreased.The rate of cholesterol efflux and mRNA and protein expressions of ABCA1 were significantly increased by tanshinoneⅡA treatment(10–4 or 10–3 mol/L) compared with the foam cell model group.Conclusion: TanshinoneⅡA inhibits the formation of foam cells induced by ox-LDL,which is related to up-regulation of expression ABCA1.