Reduction of intracellular cholesterol accumulation in THP-1 macrophages by a combination of rosiglitazone and atorvastatin

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Abstract

Rosiglitazone and atorvastatin combination therapy has beneficial effects on both glycemic control and plasma lipid levels in type 2 diabetic patients. In the present study, we sought to determine whether this combination can also exert direct antiatherosclerotic effects in macrophages. Our results show that 2 μM rosiglitazone, alone or combined with 5 μM atorvastatin, significantly upregulated the expression of the ATP-binding cassette transporter ABCA1 and of the class B scavenger receptor CLA-1 (CD36 and LIMPII analog), both involved in cholesterol efflux from macrophages. On the other hand, the combination with atorvastatin attenuated the inductive response elicited by rosiglitazone alone on CD36 mRNA (34%, P<0.05) and protein (16%, P<0.05), while the uptake of oxidized low density lipoprotein (LDL) remained unaffected. When we examined the effects of the drugs on acetyl-LDL-induced cholesterol accumulation, we found that only the combination of atorvastatin with rosiglitazone caused a net depletion in the cholesteryl ester content of macrophages (35%, P<0.05). Our data suggest that this reduction was not mediated by effects on proteins that regulate cholesterol flux, but it may be related to the inhibition of cholesteryl ester formation elicited by the statin.

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