Key Findings:
The cellular and molecular mechanisms by which ALA may reduce the symptoms of atherosclerosis were studied in a mouse modal. ALA diminished plaque formation, plaque T cell infiltration, as well as the levels of the pro-inflammatory compounds, TNFa and VCAM-1. Levels of ALA, EPA, DPA, and DHA were increased, and AA, decreased in aortas and other tissues with flaxseed feeding. Dietary ALA and direct ALA treatment restricted T cell proliferation, differentiation, and inflammatory activity. All analyzed tissues showed reductions in the n-6/n-3 ratio which correlated with a 50% reduction in plaque area. Atherosclerotic plaque formation in ApoE2/2 mice plus a reduction in TNFa, subsequent VCAM-1 expression, and inflammatory CD3-positive T cell infiltration occurred with ALA feeding. This study showed that ALA can diminish plaque formation and restrict T cell-driven inflammation in atherosclerotic mice.
ABSTRACT:
Epidemiological studies report an inverse association between plant-derived dietary alpha-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. Eight-week-old male apolipoprotein E knockout (ApoE2/2) 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- gamma, interleukin-4, and tumour necrosis factor a (TNFa) 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 TNF a. 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. (Author’s abstract)
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