title: Dietary α-linolenic acid inhibits arterial thrombus formation, tissue factor expression, and platelet activation.
abstract: OBJECTIVE
  Plant-derived α-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.
  
  
  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-κB 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.
  
  
  CONCLUSIONS
  ALA impairs arterial thrombus formation, TF expression, and platelet activation and thereby represents an attractive nutritional intervention with direct dual antithrombotic effects.
authors.affiliation: Cardiovascular Research, Institute of Physiology, Center for Integrative Human Physiology, University of Zurich, Switzerland.
authors.forename: Erik W
authors.initials: EW
authors.lastname: Holy
authors.forename: Marc
authors.initials: M
authors.lastname: Forestier
authors.forename: Eva K
authors.initials: EK
authors.lastname: Richter
authors.forename: Alexander
authors.initials: A
authors.lastname: Akhmedov
authors.forename: Florian
authors.initials: F
authors.lastname: Leiber
authors.forename: Giovanni G
authors.initials: GG
authors.lastname: Camici
authors.forename: Pavani
authors.initials: P
authors.lastname: Mocharla
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Jürg H
authors.initials: JH
authors.lastname: Beer
authors.forename: Felix C
authors.initials: FC
authors.lastname: Tanner
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D002341:Carotid Artery Thrombosis / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D019587:Dietary Supplements; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D017962:alpha-Linolenic Acid / Q000008:administration & dosage*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D017962:alpha-Linolenic Acid; D013925:Thromboplastin; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human