How do oxidized phospholipids inhibit LPS signaling?

In 1981, Henriksen and coworkers 1 reported that oxidized LDL (oxLDL) induces cholesterol accumulation in macrophages. This observation formed the basis of the hypothesis that oxidation of LDL might be an important step in the atherogenesis process. Many subsequent studies support the oxidative modification hypothesis of atherogenesis.2–4 However, oxidation of LDL is a complex process. Both the protein and the lipid molecules of LDL can be oxidatively modified resulting in a variety of biologically active molecules. The primary targets of oxidation are the esterified polyunsaturated fatty acids in the phospholipid shell that surrounds the insoluble neutral lipids of the lipoprotein core (Figure 1A). Importantly, atherosclerotic lesions contain antigens recognized by antibodies generated against oxLDL, demonstrating the presence of oxLDL in vivo.5–7