Anti-atherosclerotic actions of azelaic acid, an end product of linoleic acid peroxidation, in mice

Background: Atherosclerosis is a chronic inflammatory disease associated with the accumulation of oxidized lipids in arterial lesions. Recently we studied the degradation of peroxidized linoleic acid and suggested that oxidation is an essential process that results in the generation of terminal products, namely mono- and dicarboxylic acids that may lack the pro-atherogenic effects of peroxidized lipids. In continuation of that study, we tested the effects of azelaic acid (AzA), one of the end products of linoleic acid peroxidation, on the development of atherosclerosis using low density lipoprotein receptor knockout (LDLr-/-) mice. Methods and results: LDLr-/- mice were fed with a high fat and high cholesterol Western diet (WD group). Another group of animals were fed the same diet with AzA supplementation (WD + AzA group). After 4 months of feeding, mice were sacrificed and atherosclerotic lesions were measured. The results showed that the average lesion area in WD + AzA group was 38% (p < 0.001) less as compared to WD group. The athero-protective effect of AzA was not related to changes in plasma lipid content. AzA supplementation decreased the level of CD68 macrophage marker by 34% (p < 0.05). Conclusions: The finding that AzA exhibits an anti-atherogenic effect suggests that oxidation of lipid peroxidation-derived aldehydes into carboxylic acids could be an important step in the body's defense against oxidative damage. (C) 2009 Elsevier Ireland Ltd. All rights reserved.