AimTo investigate the effects of homocysteine (Hcy) on cholesterol synthesis in THP-1 macrophages and its potential target loci.MethodsThe macrophages were induced by phorbol 12-myristate 13-acetate(PMA)from THP-1 mononuclear cells, and treated by 5 mmol/L Hcy for 0 h,4 h,8 h,18 h and 24 h respectively.The mRNA expression of insulin-induced gene 1 (Insigl) and 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR）were determined by reverse transcription polymerase chain reaction (RT-PCR).Intracellular total cholesterol levels were examined by enzymatic colorimetric assay.ResultsIntracellular total cholesterol level increased significantly compared with the 0 h group at 18 h and 24 h（P<0.01）after Hcy-treatment. The expression of Insigl mRNA demonstrated a time-dependent down-regulation after Hcy-treatment， 8 h, 18 h and 24 h groups had significant lower Insigl mRNA level vs 0h group(P<0.05 and P<0.01).The HMGCR mRNA expression showed obvious upregulation at 18 h and 24 h compared with the 0 h group（P<0.01）.Conclusion A potential mechanism for Hcy-induced lipid accumulation in macrophage and foam cell formation may go through the following way: Hcy down-regulates the expression of Insigl, and sequentially up-regulates the HMGCR expression, which eventually increases the cholesterol synthesis in THP-1 macrophages.