Omega-3 Fatty Acids Ameliorate Atherosclerosis by Favorably Altering Monocyte Subsets and Limiting Monocyte Recruitment to Aortic Lesions

• DOI: 10.1161/atvbaha.112.253435
• Publication Date: 2012-07-21T10:35:46Z
• Authors: Amanda L. Brown; Xuewei Zhu; Shunxing Rong; Swapnil Shewale; Jeongmin Seo; Elena Boudyguina; Abraham K. Gebre; Martha A. Alexand...; John S. Parks
• Keywords: Mice, Knockout; Chemotaxis; Macrophages; Aortic Diseases; Atherosclerosis; Monocytes; Cholesterol, Dietary; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Apolipoproteins E; 0302 clinical medicine; Dietary Supplements; Fatty Acids, Omega-3; Animals; Antigens, Ly; Echium; Female; Inflammation Mediators; Aorta; Biomarkers

Objective— Fish oil, containing omega-3 fatty acids, attenuates atherosclerosis. We hypothesized that omega-3 fatty acid–enriched oils are atheroprotective through alteration of monocyte subsets and their trafficking into atherosclerotic lesions.

Methods and Results—

Low–density lipoprotein receptor knockout and apolipoprotein E −/− mice were fed diets containing 10% (calories) palm oil and 0.2% cholesterol, supplemented with an additional 10% palm oil, echium oil (containing 18:4 n-3), or fish oil. Compared with palm oil–fed low–density lipoprotein receptor knockout mice, echium oil and fish oil significantly reduced plasma cholesterol, splenic Ly6C hi monocytosis by ≈50%, atherosclerosis by 40% to 70%, monocyte trafficking into the aortic root by ≈50%, and atherosclerotic lesion macrophage content by 30% to 44%. In contrast, atherosclerosis and monocyte trafficking into the artery wall was not altered by omega-3 fatty acids in apolipoprotein E −/− mice; however, Ly6C hi splenic monocytes positively correlated with aortic root intimal area across all diet groups. In apolipoprotein E −/− mice, fish oil reduced the percentage of blood Ly6C hi monocytes, despite an average 2-fold higher plasma cholesterol relative to palm oil.

Conclusion—

The presence of splenic Ly6C hi monocytes parallels the appearance of atherosclerotic disease in both low–density lipoprotein receptor knockout and apolipoprotein E −/− mice. Furthermore, omega-3 fatty acids favorably alter monocyte subsets independently from effects on plasma cholesterol and reduce monocyte recruitment into atherosclerotic lesions.