Effects Of Lectin-like Oxidized Low Density Lipoprotein Receptor-1 (LOX-1) On Mmp-9 In Human Monocyte-derived Macrophages

Objective:To observe how oxidized low density lipoprotein (ox-LDL) impact the expression and activity of Matrix metalloproteinase-9 (MMP-9) in human macrophages and how lectin-like oxidized low density lipoprotein receptor-1(Lox-1) act as in the course.Method:Human monocytes-derived macrophages were cultured in vitro, and the 2～6th generation were took for use. Grouping according to different concentrations of ox-LDL (20mg/L,40mg/L,80mg/L) for 24h, and to concentrations of ox-LDL (40 mg/ L) at the different time point(1h,12h,24h),with the group preincubated with polyinosinic acid .Then, detected the quantity of MMP-9mRNA and Lox-1mRNA with RT-PCR, and the MMP-9 activity was assessed by zymography analysis.Results:1) Incubated of Human monocytes-derived macrophages with different concentrations of ox-LDL (20mg/L,40mg/L,80mg/L) for 24h, then the expression of LOX-1 and MMP-9mRNA increased in a concentration-dependent fashion(P<0.05); and when Incubated of Human monocytes-derived macrophages with ox-LDL (40mg/L) for different time (1h,12h,24h), the expression of LOX-1 and MMP-9mRNA increased in a time-dependent fashion(P<0.05).2) Incubated of Human monocytes-derived macrophages with different concentrations of ox-LDL(20mg/L,40mg/L,80mg/L)for 24h,then the activity of MMP-9 increased in a concentration-dependent fashion(P<0.05); when Incubated of Human monocytes-derived macrophages with ox-LDL (40mg/L) for different time (1h,12h,24h),the activity of MMP-9 increased in a time-dependent fashion(P<0.05).3) The expression of MMP-9mRNA and the activity of MMP-9 was reduced when Lox-1 was inhibited by polyinosinic acid (P<0.05).Conclusion:The data demonstrates that oxidized low density lipoprotein increased the expression of LOX-l, MMP-9mRNA and the activity of MMP-9 in a concentration and time-dependent fashion. Lectin-like oxidized low density lipoprotein receptor-1 may be responsible for the expression of Matrix metalloproteinase-9 in the monocyte-derived macrophages, also it can decrease the activity of MMP-9 which was mediated by the oxidized low density lipoprotein. The chemical inhibitor of Lectin-like oxidized low density lipoprotein receptor-1,polyinosinic acid decreased the effect of oxidized low density lipoprotein, which mediated the expression and activity of MMP-9 ,then affects the stabilization of atherosclerotic plaques.