Lipid oxidation in atherogenesis: an overview

The 'oxidation theory' for atherosclerosis proposes that lipid and/of protein oxidation products are responsible for lesion formation/development. The major target for oxidation is suggested to be intimal low-density lipoprotein. This idea was stimulated by the pro-atherogenic properties of in vitro oxidized lipoproteins, such as stimulation of chemotaxis and sterol accumulation in macrophages, adhesion molecule expression on endothelial cells and apoptosis of several cell types. it was supported by detection of oxidation products in lesion lipoproteins, although these are (in general) less heavily oxidized and their biological activity is less rigorously defined than for their in vitro oxidized counterparts. Lesion lipids contain products generated by both enzymic and non-enzymic oxidation reactions; the majority are generated non-enzymically. The type and source of oxidant involved has been the subject of much speculation and is not resolved. The oxidation theory predicts that appropriate antioxidants will protect against atherosclerosis. Vitamin E has been used in several animal and human studies, but to date has shown little evidence of anti-atherosclerotic potential. However, lack of knowledge of the oxidant(s) driving lesion oxidation and the complexity of the anti- and pro-oxidant properties of vitamin E may explain its disappointing track record to date. These subjects require more rigorous study before the oxidation theory can be fairly tested.