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Molecular mechanism of oxLDL inducing lipid accumulation and inflammation in macrophages to promot atherosclerosis via TLR4 signaling pathway

ZHA Qing1, CAO Li-juan1*,WANG Yan-ping2, YANG Ke2, LIU Yan1   

  1. 1.Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; 2.Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Online:2017-05-28 Published:2017-05-31


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.

Key words: TLR4, macrophage, lipid accumulation, inflammation, atherosclerosis