Dietary α-linolenic Acid Diminishes Experimental Atherogenesis and Restricts T Cell-Driven Inflammation

Eur Heart J. 2011 Oct;32(20):2573-84. doi: 10.1093/eurheartj/ehq501. Epub 2011 Jan 31.

Abstract

Aims: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / diet therapy*
  • Atherosclerosis / immunology
  • Atherosclerosis / prevention & control
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Lymphocyte Activation / drug effects
  • Male
  • Mice
  • Mice, Knockout
  • Plaque, Atherosclerotic / diet therapy
  • Plaque, Atherosclerotic / immunology
  • Plaque, Atherosclerotic / prevention & control
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • alpha-Linolenic Acid / administration & dosage*
  • alpha-Linolenic Acid / pharmacology

Substances

  • alpha-Linolenic Acid