Mechanism of low-density lipoprotein oxidation

Peroxidation of LDL is thought to be important in the pathogenesis of atherosclerosis, but the mechanism by which peroxidation is initiated is uncertain. Hydroxyl radical is an initiating species formed by the reaction of transition metal ions with hydrogen peroxide and of superoxide radical with nitric oxide. However, the role of the nitric oxide radical in macrophage-mediated LDL oxidation is still uncertain. In most in vitro experiments, reactions involving preformed peroxides in the LDL are being examined rather than first-chain initiation. Superoxide and transition metal ions (which are present in advanced human arteriosclerotic lesions) can lead to peroxide decomposition and propagate LDL peroxidation. The 'seeding' peroxides in LDL could be generated by lipoxygenases (other than 5-lipoxygenase), originate from dietary fats, or be formed by endogenous peroxidation, but the possibility of artefactual formation of peroxides during prolonged LDL isolation procedures must not be disregarded.