Dietary α-linolenic acid diminishes experimental atherogenesis and restricts T cell-driven inflammation

Epidemiological studies report an inverse association between plant-derived dietary -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 (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-, interleukin-4, and tumour necrosis factor (TNF) using quantitative PCR and ELISA. Dietary ALA increased aortic tissue levels of ALA as well as of the n3 long chain fatty acids (LC n3 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. 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 n3 FA.