Dietary a-linolenic acid diminishes experimental atherogenesis and restricts T cell-driven inflammation
Dietary a-linolenic acid diminishes experimental atherogenesis and restricts T cell-driven inflammation
Year: 2011
Authors: Winnik, S. Lohmann, C. Richter, E.K. Schafer, N. Song, W.-L. Leiber, F. Mocharla, P. et. al.
Publication Name: European Heart Journal
Publication Details: Volume 32; Number 20; Pages 2573 – 2584.
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)
Alpha-linolenic acid (ALA) may provide a valuable cardioprotective alternative to marine n-3 FA for heart health. Epidemiological studies report an inverse association between dietary ALA and sudden cardiac death, acute myocardial infarction, and atherosclerotic plaque calcification. This study aims to investigate the cellular and molecular mechanisms of dietary ALA in a mouse model of atherosclerosis. The data demonstrate that dietary ALA diminishes plaque formation, plaque T cell infiltration, as well as TNFa and VCAM-1 expression using a mouse model of atherosclerosis. Dietary flaxseed increased tissue levels of ALA, EPA, DPA, and DHA, and reduced AA in aortas and other tissues. Flax also increased urinary excretion of 3-series iPs and TxB. Both dietary ALA and direct ALA treatment restricted T cell proliferation, differentiation, and inflammatory activity. All analysed tissues revealed a marked decrease in the n-6/n-3 ratio, paralleled by a 50% reduction in plaque area upon dietary ALA. In all tissues assessed, including aortic lysates, a marked increase in ALA was observed. ALA supplementation decreased atherosclerotic plaque formation in ApoE2/2 mice, paralleled by a marked reduction in TNFa, subsequent VCAM-1 expression, and inflammatory CD3-positive T cell infiltration. The results also suggest a substantial degree of chain elongation, allowing a potential indirect eicosanoid-dependent effect. Diminished AA in aortae paralleled by decreased plaque T cell counts in mice fed a high ALA diet was reported. Urinary analyses also revealed a shift towards 3-series prostanoid formation, most evident in the depressed TxB 2M/TxB 3M ratio. Altered expression profiles in T cells after long-term and short-term ALA exposure in cell culture experiments were noted. These findings indicate direct effects, most likely independent of lipid-derived mediators, i.e. eicosanoids. The authors propose that the interplay of both direct (e.g. TNFa expression) and indirect (i.e. eicosanoid-dependent) mechanisms mediate the role of ALA in atheroprotection. This study provides evidence that plant-derived dietary ALA diminishes plaque formation and restricts T cell-driven inflammation in atherosclerotic mice. Further investigation is needed in experimental and clinical studies to determine the optimal dosing of ALA, its key molecular mechanisms, and target patient populations.(Editor�s comments)
Alpha-linolenic acid (ALA) may provide a valuable cardioprotective alternative to marine n-3 FA for heart health. Epidemiological studies report an inverse association between dietary ALA and sudden cardiac death, acute myocardial infarction, and atherosclerotic plaque calcification. This study aims to investigate the cellular and molecular mechanisms of dietary ALA in a mouse model of atherosclerosis. The data demonstrate that dietary ALA diminishes plaque formation, plaque T cell infiltration, as well as TNFa and VCAM-1 expression using a mouse model of atherosclerosis. Dietary flaxseed increased tissue levels of ALA, EPA, DPA, and DHA, and reduced AA in aortas and other tissues. Flax also increased urinary excretion of 3-series iPs and TxB. Both dietary ALA and direct ALA treatment restricted T cell proliferation, differentiation, and inflammatory activity. All analysed tissues revealed a marked decrease in the n-6/n-3 ratio, paralleled by a 50% reduction in plaque area upon dietary ALA. In all tissues assessed, including aortic lysates, a marked increase in ALA was observed. ALA supplementation decreased atherosclerotic plaque formation in ApoE2/2 mice, paralleled by a marked reduction in TNFa, subsequent VCAM-1 expression, and inflammatory CD3-positive T cell infiltration. The results also suggest a substantial degree of chain elongation, allowing a potential indirect eicosanoid-dependent effect. Diminished AA in aortae paralleled by decreased plaque T cell counts in mice fed a high ALA diet was reported. Urinary analyses also revealed a shift towards 3-series prostanoid formation, most evident in the depressed TxB 2M/TxB 3M ratio. Altered expression profiles in T cells after long-term and short-term ALA exposure in cell culture experiments were noted. These findings indicate direct effects, most likely independent of lipid-derived mediators, i.e. eicosanoids. The authors propose that the interplay of both direct (e.g. TNFa expression) and indirect (i.e. eicosanoid-dependent) mechanisms mediate the role of ALA in atheroprotection. This study provides evidence that plant-derived dietary ALA diminishes plaque formation and restricts T cell-driven inflammation in atherosclerotic mice. Further investigation is needed in experimental and clinical studies to determine the optimal dosing of ALA, its key molecular mechanisms, and target patient populations.(Editor�s comments)
