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Combination of n-3 polyunsaturated fatty acids reduces atherogenesis in apolipoprotein E-deficient mice by inhibiting macrophage activation.

Abstract：

BACKGROUND AND AIMS:Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are major components of n-3 polyunsaturated fatty acids (n-3 PUFAs) which inhibit atherogenesis, although few studies have examined the effects of the combination of EPA and DHA on atherogenesis. The aim of this study was to investigate whether DHA has additional anti-atherosclerotic effects when combined with EPA. METHODS:Male 8-week-old apolipoprotein E-deficient (Apoe-/-) mice were fed a western-type diet supplemented with different amounts of EPA and DHA; EPA (2.5%, w/w), low-dose EPA + DHA (2.5%, w/w), or high-dose EPA + DHA (5%, w/w) for 20 weeks. The control group was fed a western-type diet containing no n-3 PUFA. Histological and gene expression analysis were performed in atherosclerotic lesions in the aorta. To address the mechanisms, RAW264.7 cells were used. RESULTS:All n-3 PUFA treatments significantly attenuated the development and destabilization of atherosclerotic plaques compared with the control. The anti-atherosclerotic effects were enhanced in the high-dose EPA + DHA group (p < 0.001), whereas the pure EPA group and low-dose EPA + DHA group showed similar results. EPA and DHA additively attenuated the expression of inflammatory molecules in RAW264.7 cells stimulated with LPS. DHA or EPA + DHA suppressed LPS-induced toll-like receptor 4 (TLR4) expression in lipid rafts on RAW264.7 cells (p < 0.05). Lipid raft disruption by methyl-β-cyclodextrin suppressed mRNA expression of inflammatory molecules in LPS-stimulated macrophages. CONCLUSION:n-3 PUFAs suppressed atherogenesis. DHA combined with EPA had additional anti-inflammatory effects and inhibited atherogenesis in Apoe-/- mice. The reduction of TLR4 expression in lipid rafts in macrophages by DHA might be involved in this mechanism, at least partially.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Takashima A,Fukuda D,Tanaka K,Higashikuni Y,Hirata Y,Nishimoto S,Yagi S,Yamada H,Soeki T,Wakatsuki T,Taketani Y,Shimabukuro M,Sata M

doi

10.1016/j.atherosclerosis.2016.10.002

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

142-150

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(16)31405-8

journal_volume

254

pub_type

杂志文章

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Combination of n-3 polyunsaturated fatty acids reduces atherogenesis in apolipoprotein E-deficient mice by inhibiting macrophage activation.