Effects Of Simvastatin On Sr-a1 Expression And Foam Formation Of Human Thp-1 Derived Macrophage

Objective: To investigate the effect of simvastatin on phorbol 12-myristate 13-acetate (PMA)-induced lipid accumulation and scavenger receptor A expression in THP-1 macrophages.To probe the possible mechanism of anti-atherosclerosis of simvastatin.Methods: Macrophages were derived from Human monocyte lines THP-1 by PMA induce.THP-1 macrophages were incubated with 50mg/L ox-LDL into foam cells..THP-1 macrophages were coincubated with 50mg/L ox-LDL and simvastatin at different concentration (1umol/L,5umol/L,10umol/L) respectively for 24h. THP-1 macrophages were incubated without ox-LDL and simvastatin as the control groups.The course of macrophage differentiating foam cell by ox-LDL stimulating were observed.Oil Red O staining was used to observe the intracellular lipid droplets.Cellular total cholesterol was determined by high performance liquid chromatography(HPLC) analysis. The levels of scavenger receptor A mRNA in all groups were observed by semiquantitative RT-PCR.We observed the levels of scavenger receptor A in all groups by Western-blot.Results: It was observed that Monocyte lines THP-1 differentiate into macrophages by inducer PMA at microscope.Cellular characteristics were changed: from suspension to pasting wall: from round shape to ellipse , shuttle , irregular shape.Incubated by ox-LDL,Maerophages differentiated into foamcells: there were a load of lipid droplet through Oil red O staining.Oil red O staining showed the more lipid droplets were in 50mg/L oxLDL groups than control,and the less lipid droplets were in simvastatin groups than 50mg/L oxLDL groups. Oil Red O staining showed intracellular droplets were minor with the presence of simvastatin.HPLC analysis demonstrated the ratios of cellular CE/TC were (59.96±1.40)%,( 54.32±1.39 ) %,( 45.64±2.39 ) %,( 39.31±1.56 ) % at different concerntrations of simvastatin and (12.62±1.08)% in control.The chang of the levels of scavenger receptor A mRNA:The levels of scavenger receptor A mRNA in simvastatin group were lower than 50mg/L oxLDL groups significantly(P﹤0.05).Interfered by simvastatin,the levels of scavenger receptor A mRNA were decreased.The degree of degression was correlated positively to drugs concentration.The chang of the levels of scavenger receptor A proteins:The levels of scavenger receptor A proteins in simvastatin group were lower than 50mg/L oxLDL groups significantly(P﹤0.05).Interfered by simvastatin,the levels of scavenger receptor A mRNA were decreased.The degree of degression was correlated positively to drugs concentration.Conclusion:1. Simvastatin may decrease PMA-induced lipid accumulation in THP-1 macrophages.2. Simvastatin may downregulate PMA-induced SR-A expression in THP-1 macrophages.3.The mechanism of simvastatin anti-atherosclerosis may be its decreasing lipid accumulation in foam cells and downregulating expression of scavenger receptor A of macrophages.