Abstract 4941: Dietary Alpha-Linolenic Acid Supplementation Inhibits Thrombus Formation in vivo

Abstract

Background. Considering the reduced availability of marine derived long-chain n-3 fatty acids (n-3 FA), the use of the plant-derived n-3 FA α -linolenic acid (ALA) may constitute an attractive cardioprotective alternative. However, despite promising epidemiological data, the effect of dietary ALA supplementation on arterial thrombus formation remains unknown. Methods and Results. 8 week-old male C57Bl/6 mice were fed either a high ALA (7.3g%) or low ALA (0.03g%) diet for 2 weeks. Mice fed a high ALA diet showed delayed carotid artery thrombus formation in a mouse photochemical injury model as compared to mice on a low ALA diet (68±6 vs 40±4.2 minutes; n=7; p<0.05). High dietary ALA supplementation impaired platelet aggregation as determined by whole blood aggregometry in isolated murine platelets (n=5; p<0.005), without affecting PTT and aPTT clotting times (n=7; p=NS). Mice on the high ALA diet exhibited reduced vascular tissue factor (TF) expression and activity, as well as reduced vascular NF kappa B activity (n=7; p<0.05). In human endothelial, vascular smooth muscle, and peripheral blood mononuclear cells ALA (10 –30 μ mol/l) inhibited tumor necrosis factor (TNF)- α and thrombin induced TF expression as well as surface activity (n=4; p<0.01). Real time PCR and analysis of TF promoter activation demonstrated that ALA mediated inhibition of endothelial TF expression occurred at the transcriptional level involving the MAP kinases p38, ERK and JNK1/2 (−62%,−55% and −28% versus TNF- α alone; n=3; p<0.05). In endothelial cells ALA impaired TNF-á induced I kappa B-á degradation and NF kappa B activation (n=3; p<0.05). Conclusions. A diet rich in plant-derived ALA inhibits arterial thrombus formation via impaired platelet aggregation and reduced TF expression. Hence, dietary ALA supplementation represents an attractive antithrombotic nutritional supplement.