Dietary α-Linolenic Acid Inhibits Arterial Thrombus Formation, Tissue Factor Expression, and Platelet Activation

Objective-Plant-derived alpha-linolenic acid (ALA) may constitute an attractive cardioprotective alternative to fish-derived n-3 fatty acids. However, the effect of dietary ALA on arterial thrombus formation remains unknown. Methods and Results-Male C57Bl/6 mice were fed a high-ALA or low-ALA diet for 2 weeks. Arterial thrombus formation was delayed in mice fed a high-ALA diet compared with those on a low-ALA diet (n = 7; P < 0.005). Dietary ALA impaired platelet aggregation to collagen and thrombin (n = 5; P < 0.005) and decreased p38 mitogen-activated protein kinase activation in platelets. Dietary ALA impaired arterial tissue factor (TF) expression, TF activity, and nuclear factor-kappa B activity (n = 7; P < 0.05); plasma clotting times and plasma thrombin generation did not differ (n = 5; P = not significant). In cultured human vascular smooth muscle and endothelial cells, ALA inhibited TF expression and activity (n = 4; P < 0.01). Inhibition of TF expression occurred at the transcriptional level via the mitogen-activated protein kinase p38 in smooth muscle cells and p38, extracellular signal-regulated kinases 1 and 2, and c-Jun N-terminal kinases 1 and 2 in endothelial cells. Conclusion-ALA impairs arterial thrombus formation, TF expression, and platelet activation and thereby represents an attractive nutritional intervention with direct dual antithrombotic effects. (Arterioscler Thromb Vasc Biol. 2011;31:1772-1780.)