Omega 3 Polyunsaturated Fatty Acids Suppress the Development of Aortic Aneurysms Through the Inhibition of Macrophage-Mediated Inflammation.
BACKGROUND
Dietary intake of ω3 polyunsaturated fatty acids (ω3-PUFAs) reduces progression of atherosclerosis and prevents future cardiovascular events. Macrophages are key players in the pathogenesis of aortic aneurysm. The effects of ω3-PUFAs on abdominal aortic aneurysm (AAA) formation and macrophage-mediated inflammation remain unclear. METHODS AND RESULTS: The AAA model was developed by angiotensin II infusion in apolipoprotein E-deficient mice. Mice were supplemented with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). The development of AAA lesions and macrophage infiltration in the aorta were analyzed. Gene expression of inflammatory markers in aortic tissues and peritoneal macrophages were measured by using quantitative polymerase chain reaction. AAA formation and macrophage infiltration were significantly suppressed after EPA and DHA administration. EPA administration and DHA administration significantly decreased the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β, matrix metalloproteinases (MMP)-2, MMP-9, and vascular cell adhesion molecule-1 in the aortas. The expression of arginase 2, which is a marker of pro-inflammatory macrophages, was significantly lower and that of Ym1, which is a marker of anti-inflammatory macrophages, and was significantly higher after EPA and DHA administration. The same trends were observed in peritoneal macrophages after EPA and DHA administration.


CONCLUSIONS
Dietary intake of EPA and DHA prevented AAA development through the inhibition of aortic and macrophage-mediated inflammation.
Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine.
Takuma
T
Yoshihara
Kazunori
K
Shimada
Kosuke
K
Fukao
Eiryu
E
Sai
Yayoi
Y
Sato-Okabayashi
Rie
R
Matsumori
Tomoyuki
T
Shiozawa
Hamad
H
Alshahi
Tetsuro
T
Miyazaki
Norihiro
N
Tada
Hiroyuki
H
Daida
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D001119:Arginase / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D015850:Interleukin-6 / Q000235:genetics; D019751:Intramolecular Transferases / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000097:blood / Q000737:chemistry; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D001057:Apolipoproteins E; D029681:Arabidopsis Proteins; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015525:Fatty Acids, Omega-3; D018836:Inflammation Mediators; D015850:Interleukin-6; D008055:Lipids; C481673:Arg2 protein, mouse; D001119:Arginase; D019751:Intramolecular Transferases; C568454:marneral synthase, Arabidopsis