Winnik, S; Lohmann, C; Richter, E K; Schäfer, N; Song, W L; Leiber, F; Mocharla, P; Hofmann, J; Klingenberg, R; Borén, J; Becher, B; Fitzgerald, G A; Lüscher, T F; Matter, C M; Beer, J H (2011). Dietary α-linolenic acid diminishes experimental atherogenesis and restricts T cell-driven inflammation. European Heart Journal, 32(20):2573-2584.
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Epidemiological studies report an inverse association between plant-derived dietary α-linolenic acid (ALA) and cardiovascular events. However, little is known about the mechanism of this protection. We assessed the cellular and molecular mechanisms of dietary ALA (flaxseed) on atherosclerosis in a mouse model.
METHODS AND RESULTS:
Eight-week-old male apolipoprotein E knockout (ApoE(-/-)) mice were fed a 0.21 % (w/w) cholesterol diet for 16 weeks containing either a high ALA [7.3 % (w/w); n = 10] or low ALA content [0.03 % (w/w); n = 10]. Bioavailability, chain elongation, and fatty acid metabolism were measured by gas chromatography of tissue lysates and urine. Plaques were assessed using immunohistochemistry. T cell proliferation was investigated in primary murine CD3-positive lymphocytes. T cell differentiation and activation was assessed by expression analyses of interferon-γ, interleukin-4, and tumour necrosis factor α (TNFα) using quantitative PCR and ELISA. Dietary ALA increased aortic tissue levels of ALA as well as of the n-3 long chain fatty acids (LC n-3 FA) eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. The high ALA diet reduced plaque area by 50% and decreased plaque T cell content as well as expression of vascular cell adhesion molecule-1 and TNFα. Both dietary ALA and direct ALA exposure restricted T cell proliferation, differentiation, and inflammatory activity. Dietary ALA shifted prostaglandin and isoprostane formation towards 3-series compounds, potentially contributing to the atheroprotective effects of ALA.
Dietary ALA diminishes experimental atherogenesis and restricts T cell-driven inflammation, thus providing the proof-of-principle that plant-derived ALA may provide a valuable alternative to marine LC n-3 FA.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Experimental Immunology|
|DDC:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||28 Feb 2012 14:46|
|Last Modified:||27 Nov 2013 22:09|
|Publisher:||Oxford University Press|
|Citations:||Web of Science®. Times Cited: 11|
Scopus®. Citation Count: 13
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