Fig. 1.

Mechanisms of LDL oxidation in the arterial wall. Upon entry in the subendothelial space LDL particles are exposed to local oxidative stress arising from the presence of cell-associated enzymes, including NADPH oxidase, lipoxygenases and myeloperoxidase, as well as from transition metal ions. Oxidants produced by these entities may oxidize LDL to different degrees. Whereas NADPH oxidase and lipoxygenases only lead to the formation of minimally oxidized LDL, myeloperoxidase and NADPH oxidase combined with NO synthase oxidize LDL extensively. The minimally oxidized LDL is predominantly characterized by the presence of oxidized lipids, whilst extensive oxidation of both protein and lipid components constitutes the hallmark of extensively oxidized LDL. Minimally oxidized LDL displays low affinity to macrophage scavenger receptors and can readily return to the bloodstream. Locally, minimally oxidized LDL induces inflammatory activation involving chemokine and cytokine production and recruitment of inflammatory cells, which in turn increases chemokine and cytokine accumulation. As a result, lipid oxidation proceeds ending in the formation of heavily oxidized and fragmented apo B. Such extensively oxidized LDL are readily taken up by macrophages via scavenger receptors leading to the formation of foam cells.

LDL, low density lipoprotein; oxLDL, oxidized LDL; apo, apolipoprotein; oxPL, oxidized phospholipid; LOOH, lipid hydroperoxide.