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

Figure 1

Different players in atherosclerosis. Increased LDL enters the cell via micropinocytosis and is converted into oxLDL. Additionally, after digesting oxLDL by APC, TCRs detect APO-B100 as an autoantigen by MHC2, leading to the release of IL-17 and IFN-γ. Absorbed cholesterol crystals can activate NOD, LRR, and pyrin domain-containing protein 3 (NLRP3) inflammasome, causing the production of IL-1β. Furthermore, monocytes pass through the endothelium and differentiate into scavenger receptors, including SK-A, SK-B1, CD36, CD68, LOX-1, and SR-PSOX. Macrophages will be enabled to absorb more oxLDL. Meanwhile, granular proteins such as azurocidin, cathepsin G, and α-defensin produced by neutrophils, facilitate the conversion of macrophages to foam cells. Additionally, the binding of oxLDL to LOX-1 leads to the release of growth factors that can increase the proliferation of smooth muscle cells. In summary, the aggregation of foam cells can create fatty streaks, which is the initial step in the formation of atherosclerotic plaque. LDL, low-density lipoprotein; oxLDL, oxidized low-density lipoprotein; APC, antigen-presenting cell; TCRs, T-cell receptors; APO-B100, apolipoprotein B-100; MHC2, major histocompatibility complex class II; IL-17, interleukin-17; IFN-γ, interferon-gamma; NLRP3, NOD-, LRR-, and pyrin domain-containing protein 3; IL-1β, interleukin-1β; SK-A, scavenger receptor class A; SK-B1, scavenger receptor class B type 1; CD36, cluster of differentiation 36; CD68, cluster of differentiation 68; LOX-1, lectin-like oxidized low-density lipoprotein receptor-1; SR-PSOX, scavenger receptor that binds phosphatidylserine and oxidized lipoproteins.