Atherosclerosis and Toll-Like Receptor4 (TLR4), Lectin-Like Oxidized Low-Density Lipoprotein-1 (LOX-1), and Proprotein Convertase Subtilisin/Kexin Type9 (PCSK9)

Figure 2

TLR4 signaling cascade. Circulating LBP recognizes LPS in the plasma and brings it to CD14. This aids the loading of LPS onto the LPS receptor complex, which is composed of dimerized TLR4 receptors and two molecules of the extracellular adapter MD-2. Subsequent signals activated by TLR4 can be subdivided into those dependent on MyD88, which occur early, and those independent of MyD88, which occur later and use the adapters TRIF and TRAM. LPS signaling leads to the early activation of NF-κB, IRF3, and MAPK kinase pathways, which are mediated by MyD88. After the subsequent activation and phosphorylation of IRAK, TRAF6 becomes activated, which gives rise to the expression of numerous pro-inflammatory genes. As a later response to LPS, TLR4 gives rise to the activation of TRAF6 and TBK1, an event mediated by the adapters; TRIF and TRAM. LPS, lipopolysaccharide; LBP, LPS-binding protein; MyD88, myeloid differentiation factor 88; IRAK, IL-1R-associated kinase; TLR, Toll-like receptor; TRAF, tumor necrosis factor receptor-associated factor; TRIF, Toll/IL-1R domain-containing adaptor-inducing IFN-β; IKK, inhibitor of nuclear factor-κB (IκB) kinase.