Scavenger Receptor A, The Role Of The Inflammatory Response In The Artery Atherosclerosis And Drug Intervention, And Clinical Research

Objective To study the change of expression of scavenger receptor A and secretion of monocyte chemoattactant protein-1(MCP-1) in the course of monocyte lines THP-1 differentiating macrophages and foam cells using atorvastatin and Ginkgo biloba extract (GbE) to interfere on them.To probe the important role of scavenger receptor A and MCP-1 in atherogenesis, their realationship and the mechanism of anti-atherosclerosis of atorvastatin and GbE.Methods Macrophages were derived from Human monocyte lines THP-1 by PMA induce. Its were divided into 4 groups: control, ox-LDL, ox-LDL+atorvastatin(then divided into 3 groups: low,mid,high concentration), ox-LDL+ GbE(then divided into 3 groups: low,mid,high concentration). The course of macrophage differentiating foam cell by ox-LDL stimulating were observed. Concentration of MCP-1 in cell substratum were measured by ELISA.The levels of scavenger receptor A mRNA in all groups were compared by semiquantitative RT-PCR. Macropahges were incubated with Dil-Ac-LDL which was specific ligand,and we observed the levels of scavenger receptor A in all groups by fluorescent microscope. We analysed the relationship between concentration of MCP-1 and the activity of scavenger receptor A.Results It was observed that Monocyte lines THP-1 differentiated 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, Macrophages differentiated into foam cells:there were a load of lipid droplet through Nile red staining.The change of concentration of MCP-1: Compared to the control, the concentration of MCP-1 were higher, significantly higher after 6 hours, reached to peak at 12 hours, decreased after 24h. Downregulation of concentration of MCP-1 were depedented on dosage of atorvasatin and GbE.The more drug dosage increased, the lower the levels of MCP-1 decreased.The change of the levels of scavenger receptor A mRNA:The levels of scavenger receptor A mRNA in ox-LDL group were higher than the control significantly (p<0.0\) . Interfered by atrovatain and GbE, The levels of scavenger receptor A mRNA were decreased.The degree of degression was correlated positivly to drugs concentration.The change of the activity of scavenger receptor A proteins: The activity of scavenger receptor A proteins in ox-LDL group were higher than the control significantly (/><0.01) . Interfered by atrovatain and GbE, The activity of scavenger receptor A protein were decreased. The degree of degression was correlated positivly to drugs concentration.The relationship between activity of scavenger receptor A proteins and concentation of MCP-1: The activity of scavenger receptor A proteins in all groups was correlated positively concentation of MCP-1 at 12h after medicating ox-LDL (r=0.681,p<0.01) .Conclusions(1) Foam cells model may be made successfully which derived from Humanmonocyte lines THP-1 by PMA inducing and ox-LDL incubating.(2) The secretion of MCP-1 increased in the course of Human monocyte lines THP-1 differentitating into foam cells.(3) The expression of scavenger receptor A increased in the course of Human monocyte lines THP-1 differentitating into foam cells.(4) The activity of scavenger receptor A protein in all groups was correlated positively concentation of MCP-1.(5) The mechanism of atorvastain and GbE anti-atherosclerosis may be its inhibiting secretion of MCP-1 and expression of scavenger receptor A of macrophages.(6) This subject supplied experimental basis for the rational therapy of atherosclerosis in clinics.