[Role of lipid peroxidation in the formation of atheroma]

The demonstration that lipid peroxidation (enzymatic or non enzymatic oxidation of polyunsaturated fatty acids) is involved and plays a pathophysiological role (in relation to the metabolic pathways of prostaglandins, leukotrienes and to others inflammation-related events) in the initiation of arteriosclerotic plaques is a breakthrough in the pathogenesis of atheroma. Macrophages play a central role in this mechanism. Indeed foam cells are macrophages loaded with oxidized low density lipoproteins (LDL). These oxidized LDL are preferentially recognized by macrophages thanks to their scavenger receptor. The role of such foam cells in the initiation and development of atheroma is well known. The formation of arteriosclerotic plaques results in important endothelial alterations, and endothelial cells lose their protective ability to prevent platelet aggregation and related thrombotic events. Inflammation and thrombosis are overlapping phenomena which are mediated by common cells (platelets, polymorphonuclear leucocytes, monocytes, macrophages, endothelial cells). During the activation of such inflammatory cells a number of eicosanoids are produced, and the profile of such metabolites is largely controlled by cellular interactions. In addition these inflammatory cells have the ability to produce oxygen free radicals, and initiate non enzymatic lipid peroxidation.