Oxidative modification of low-density lipoproteins in atherothrombosis

Oxidative modification of LDL may occur via mechanisms, which are either de pendent or independent of lipid peroxidation. Peroxidation of lipids in LDL , either initiated by radicals or catalysed by myeloperoxidase, results in the generation of aldehydes which substitute lysine residues in the apolipo protein B- 100 moiety and thus in the generation of oxidised LDL. Phospholi pase activity, prostaglandin synthesis and platelet adhesion/activation are associated with the release of aldehydes which induce oxidative modificati ons of LDL in the absence of lipid peroxidation and thus in the generation of malondialdehyde-modified LDL. Recently, we have demonstrated an associat ion between coronary artery disease and increased plasma levels of oxidised LDL. The increase of circulating oxidised LDL is most probably due to back diffusion of oxidised LDL from the atherosclerotic arterial wall in the blo od and is independent of plaque instability. Indeed, plasma levels of oxidi sed LDL were very similar in patients with stable coronary artery disease a nd in patients with acute coronary syndromes. Acute coronary syndromes were , however, associated with increased release of malondialdehyde-modified LD L that was independent of necrosis of myocardial cells. Indeed, plasma leve ls of malondialdehyde-modified LDL were very similar in patients with unsta ble angina and patients with acute myocardial infarction, in contrast with levels of troponin I which were significantly higher in acute myocardial in farction patients. These data suggest that oxidised LDL is rather a marker of coronary atherosclerosis whereas malondialdehyde-modified LDL is rather a marker of plaque instability and atherothrombosis. At present, in the abs ence of prospective studies, the causative role of oxidatively modified LDL in atherothrombosis is, however, not established.