The effects of ox-LDL in human atherosclerosis may be mediated in part via the TLR4 pathway
Objective To explore the relationship between the effects of oxidized low density lipoprotein (ox-LDL) in human atherosclerosis and the expression of Toll-like receptor 4 (TLR4). Methods Before and after transfection with the TLR4 siRNA plasmid expression vectors, human monocytic U937 cells were stimulated with ox-LDL of the different final concentrations. The TLR4 expression was measured by flow eytometry and real time PCR; NF-κB activity and the concentrations of MCP-Ⅰand IL-8 were detected by EHSA. Results The positive rate and the mean mRNA copy number of TLR4 increased in response to ox-LDL. Simultaneously, NF-κB relative activity and the concentrations of MCP-1 and IL-8 in cell supematant were up-regulated by ox-LDL in a dose-de- pendent manner(P0.05). TLR4 expression was inhibited by siRNA plasmid expression vectors, and NF-κB ac- tivity and the secretion of MCP-1 and IL-8 in response to ox-LDL were significantly lower in the group that TLR4 expression has been inhibited than that in the group that TLR4 expression has not been inhibited(P0.05). Con- clusion The atherogenic effects of ox-LDL could be mediated in part via the TLR4 pathway. And inhibition of TLR4 expression may down-regulate the NF-κB activity and MCP-1 and IL-8 secretion in monocytes by ox-LDL, resulting in the alleviation of the progress of atherosclerosis.