Oxidized lipids.

Abstract

The addition of oxygen to lipids, in response to inflammatory and mitogenic stimuli, is an important process developed by biological systems to generate a wide spectrum of compounds both by enzymatic and non-enzymatic mechanisms. These oxidized lipids may serve as messengers for communication both within and between cells or may induce structural and metabolic changes in the cell. Since chronic inflammation has been proposed as an important risk factor for coronary events by making atherosclerotic plaques prone to rupture, extensive studies have been conducted to probe the involvement of the different pathways of lipid oxidation in the pathogenesis of coronary heart disease. The oxidation of arachidonic acid and 2-arachidonylglycerol through the activity of cyclooxygenase-2 may play a role in plaque instability through dysregulation of vascular tone and induction of endothelial dysfunction. Moreover, two families of biologically active mediators formed by free-radical catalyzed oxidation of arachidonic acid and phosphatidylcholine, i.e. isoprostanes and platelet activating factor-like lipids, respectively, may be involved. Clarification of the metabolic steps of lipid oxidation altered in unstable coronary artery disease will be of valuable help in identifying new cardiovascular markers for the prediction of the long-term risk of death from cardiac causes. The integration of this information with the presence of mutations in the genes encoding the enzymatic machinery of lipid oxidation will be useful in the selection of patients with increased risk of myocardial infarction.