TY - JOUR
T1 - Omega-3 fatty acids ameliorate atherosclerosis by favorably altering monocyte subsets and limiting monocyte recruitment to aortic lesions
AU - Brown, Amanda L.
AU - Zhu, Xuewei
AU - Rong, Shunxing
AU - Shewale, Swapnil
AU - Seo, Jeongmin
AU - Boudyguina, Elena
AU - Gebre, Abraham K.
AU - Alexander-Miller, Martha A.
AU - Parks, John S.
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
KW - Ly6C
KW - echium oil
KW - fish oil
KW - inflammation
KW - monocytosis
KW - omega-3 fatty acids
UR - http://www.scopus.com/inward/record.url?scp=84865524281&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865524281&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.112.253435
DO - 10.1161/ATVBAHA.112.253435
M3 - Article
C2 - 22814747
AN - SCOPUS:84865524281
SN - 1079-5642
VL - 32
SP - 2122
EP - 2130
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 9
ER -