Objective · To investigate the possible role of TLR4 signaling pathway in the mediation of atherosclerosis. Methods · TLR4 were knocked down via transfection with TLR4-specific siRNA, and the lipid accumulation was further detected in control and TLR4-knockdown groups by oil red O staining. The expression of CD36 and Lectin-like oxLDL receptor 1 (LOX-1) in macrophages were detected by Western blotting to investigate the role of TLR4 in the expression of oxLDL-related receptors. Cytokines such as interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein 1 (MCP-1), and matrix metalloproteinase-9 (MMP-9) were tested by ELISA to confirm the possible role of TLR4 in the secretion of inflammatory factors. Results · Macrophages
(namely CD68+ cells) were found to accumulate within atherosclerosis plaques with TLR4 highly expressed on the surface of macrophages; the stimulation with oxLDL promoted the lipid accumulation (P<0.01), the secretion of inflammatory factors (P<0.01), and the expression of CD36 and LOX-1. The oxLDL-associated expression of CD36 was decreased but the expression of LOX-1 was not affected. The knockdown of TLR4 inhibits oxLDL-induced lipid accumulation (P<0.01)and inflammatory cytokines (IL-6, IL-8, MCP-1 and MMP-9) secretion (P<0.01). Conclusion · TLR4 signaling pathway possibly promotes the lipid accumulation and the secretion of inflammatory factors via up-regulating the expression of CD36 to affect the formation and development of atherosclerosis.