title: Dietary α-linolenic acid diminishes experimental atherogenesis and restricts T cell-driven inflammation.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiovascular Research,  Institute of Physiology, Zurich University, Winterthurerstrasse 190, CH-8057 Zurich,  Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Winnik
authors.forename: Christine
authors.initials: C
authors.lastname: Lohmann
authors.forename: Eva K
authors.initials: EK
authors.lastname: Richter
authors.forename: Nicola
authors.initials: N
authors.lastname: Schäfer
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Song
authors.forename: Florian
authors.initials: F
authors.lastname: Leiber
authors.forename: Pavani
authors.initials: P
authors.lastname: Mocharla
authors.forename: Janin
authors.initials: J
authors.lastname: Hofmann
authors.forename: Roland
authors.initials: R
authors.lastname: Klingenberg
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
authors.forename: Garret A
authors.initials: GA
authors.lastname: Fitzgerald
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Christian M
authors.initials: CM
authors.lastname: Matter
authors.forename: Jürg H
authors.initials: JH
authors.lastname: Beer
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000178:diet therapy* / Q000276:immunology / Q000517:prevention & control; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000178:diet therapy / Q000276:immunology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D017962:alpha-Linolenic Acid / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D017962:alpha-Linolenic Acid