Molecular mechanism of oxLDL inducing lipid accumulation and inflammation in macrophages to promot atherosclerosisvia TLR4 signaling pathway
10.3969/j.issn.1674-8115.2017.05.008
- VernacularTitle:oxLDL通过TLR4诱导脂质累积和炎症反应促进动脉粥样硬化的分子机制
- Author:
Lijuan CAO
;
Yanping WANG
;
Ke YANG
;
Yan LIU
- Keywords:
TLR4;
macrophage;
lipid accumulation;
inflammation;
atherosclerosis
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2017;37(5):611-615
- CountryChina
- Language:Chinese
-
Abstract:
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 andLectin-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 atherosclerosisplaques 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.
