Effects Of Ezetimibe Combined With Rosiglitazone On Cholesterol Contents In Vascular Smooth Muscle-derived Foam Cells Via The LXR?-ABCA1 Pathway

Objective:To study the effect of ezetimibe combined with rosiglitazone on cholesterol contents of foam cells derived from vascular smooth muscle cells(VSMCs)induced by oxidized low density lipoprotein(ox-LDL),and to explore the role of liver X receptor alpha(LXR?)-ATP binding cassette transporter A1(ABCA1)pathway in the process.Methods:Normal cultured rat VSMCs were taken as the blank control group.Smooth muscle-derived foam cells induced by ox-LDL(50ug/ml)were divided into foam cells group,different concentrations of ezetimibe groups(3umol/L,10umol/L and 30umol/L),rosiglitazone group(25umol/L)and combined group(30umol/L ezetimibe + 25 umol/L rosiglitazone).Oil red O staining was used to identify the model of foam cells.Real-time PCR was used to detect the mRNA levels of LXR? and ABCA1 in each group,and Western blot was used to detect the relevant protein levels.The contents of total cholesterol(TC)and free cholesterol(FC)in each group were detected by the Enzyme Fluorescence method.Results:1.Compared with the blank control group,the mRNA expressions of LXR? and ABCA1 were significantly decreased in the foam cells group(P<0.05);Compared with the foam cells group,the mRNA expressions of LXR? and ABCA1 were upregulated by different concentrations of ezetimibe in a concentration-dependent manner(P<0.05).2.Compared with the blank control group,the mRNA and protein expressions of LXR? and ABCA1 were significantly decreased in the foam cells group(P<0.05);Compared with the foam cells group,the mRNA and protein expressions of LXR? and ABCA1 were increased in the ezetimibe 30umol/L group,rosiglitazone group and combined group(P<0.05);And the mRNA and protein expressions of LXR? and ABCA1 were further increased in the combined group compared with ezetimibe 30umol/L group and rosiglitazone group(P<0.05).3.Compared with the blank control group,the contents of TC,FC and cholesteryl ester(CE)were significantly decreased in the foam cells group(P<0.05),and CE/TC>50%;Compared with the foam cells group,the contents of TC,FC and CE were decreased,the ratio of CE/TC was reduced in the ezetimibe 30umol/L group,rosiglitazone group and combined group(P<0.05);And the contents of TC,FC and CE were further decreased,as well as the ratio of CE/TC was further reduced in the combined group compared with ezetimibe 30umol/L group and rosiglitazone group(P<0.05).Conclusion:Ezetimibe and rosiglitazone can promote ABCA1 mediated reverse cholesterol transport via LXR?-ABCA1 pathways in vascular smooth muscle-derived foam cells,and reduce the accumulation of cholesterol in the cells.Moreover,the combination of both can further increase the expression of LXR? and ABCA1,and promote cholesterol efflux,significantly reduce the intracellular cholesterol contents.