Homocysteine Promotes Macrophage Foam Cell Formation By Interrupting Reverse Cholesterol Transport

Objective To investigate the effect of different doses of homocysteine on macrophage foam cell formation,and discuss the involvement of LXRα in homocysteine-mediated lipid metabolism disorders.Methods The THP-1 monocytes were cultured with phorbol myristateacetate(PMA) and oxidized low-density lipoprotein(ox-LDL)to duplicate the foam cell model,then treated by 0,50,100 and 200μmol/L Hcy for 24 h.Hcy 0μmol/Lworked as the control.The formation of the foam cells were analysized by the oil red O staining.The intracellular total cholesterol( TC),freecholesterol( FC) and cholesterol ester( CE) were quantified by enzymatic endpoint determination method,in order to observe the effects of different doses of Hcy on lipid assay in foam cells.The expression of LXRα protein was observed by the immunocytochemical detection.The effects of different concentrations of Hcy on the expression of LXRα m RNA in foam cells were detected by RT-PCR.Rusults Compared with the control group,increased Hcy promated the formation of foam cells markedly which was indicated by oil red O staining.The percentage the positive staining cells in the experimental groups(50,100 and 200μmol/L) was higher than that in the control group(P<0.05), and the 100μmol/L Hcy reached the most significant one. With the treatment of different concentrations of Hcy,the quantity of TC FC and CE were increased in foam cells when compared with control group(P<0.05).Immunohistochemical detection indicated that the expression of LXRα protein in all experimental groups were lower than that of the control group(P<0.05),and the 100μmol/L Hcy treated group was the most significant one. The results of RT-PCR indicated that the expression of LXRα m RNA was significantly decreased in the experimental groups when compared with the control(P<0.05).Conclusions Hcy promoted the accumulation of cholesterol in macrophages and then the formation of foam cells.Lower expression of LXRα might be the mechanisms of homocysteine-induced lipid metabolism disorders.