Effects Of Rosiglitazone On Expression Of Acyl-coenzyme A Cholesterol Acyltransferase1and ATP-binding Cassette Transporter A1in Foam Cells

Objective To investigate the effects of rosiglitazone on cholesterol content and the expressions of acyl-CoA:cholesterol acyltransferase1(ACAT-1) and ATP binding cassette transporter A-1(ABCA-1)in RAW264.7macropgage-derived foam cells, and explore the effects and mechanisms of rosiglitazone on foam cells formation, so as to provide theory basis of rosiglitazone preventing atherosclerosis in clinical.Methods (1) Establishment of foam cell model:RAW264.7cells were co-cultured with30mg/L oxidized low density lipoprotein (oxLDL) for48h, then the formation of foam cells were identified by oil red O staining technique.(2) Cultured RAW264.7cells were divided into5groups randomly:blank control group, cells were cultured in normal growth medium; oxLDL group, cells were co-cultured with30mg/L oxLDL for48h; oxLDL+rosiglitazone group, cells were co-cultured with30mg/L oxLDL and5μmol/L,10μmol/L,20μmol/L rosiglitazone respectively for48h.(3) The concentration of cellular total cholesterol (TC) and free cholesterol (FC) was measured by using cholesterol kit, and the content of cholesterol ester (CE) was acquired by subtracting the FC from TC.(4) The protein expressions of ACAT-1and ABCA-1were determined by western blot.Result (1) Oil red O staining showed cells in oxLDL group were stained by oil red O, but the color of cells in oxLDL+rosiglitazone group was shallower than that in oxLDL group.(2) Compared with blank control group, the content of cellular TC and FC in oxLDL group were significantly increased (P<0.05), while compared with oxLDL group, the content of cellular TC and FC in oxLDL+rosiglitazone group were significantly decreased(P<0.05) with a concentration-dependent manner.(3) Western blot analysis showed that the expression levels of ACAT-1in different concentration (5μmol/L,10μmol/L,20μmol/L) of oxLDL+rosiglitazone group were0.94±0.11,0.86±0.13,0.58±0.12respectively, the result is significantly different (P<0.05) from the oxLDL group(1.19±0.12), and the expression levels of ABCA-1expression in different concentration of oxLDL+rosiglitazone group were0.72±0.08,0.91±0.15,1.15±0.11respectively, the result also is significantly different (P<0.05) from the oxLDL group (0.63±0.05)Conclusion (1) OxLDL can transform RAW264.7cell into foam cell.(2) Rosiglitazone may decrease cholesterol accumulation in macrophage-derived foam cell by decreasing expression of ACAT-1and increasing expression of ABCA-1, so as to inhibit foam cell formation.