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.


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.
Litvinov
Dmitry
D
Division of Cardiothoracic Surgery, Ohio State University Medical Center, Columbus, OH 43210-1292, USA.
Selvarajan
Krithika
K
Garelnabi
Mahdi
M
Brophy
Larissa
L
Parthasarathy
Sampath
S
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000473:pathology* / Q000517:prevention & control; D003998:Dicarboxylic Acids / Q000627:therapeutic use*; D005260:Female; D019787:Linoleic Acid / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency
D003998:Dicarboxylic Acids; D011973:Receptors, LDL; D019787:Linoleic Acid; C010038:azelaic acid