Dietary α-Linolenic Acid Inhibits Arterial Thrombus Formation, Tissue Factor Expression, and Platelet Activation
Open accessAbstract
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. 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-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. Conclusion—: ALA impairs arterial thrombus formation, TF expression, and platelet activation and thereby represents an attractive nutritional intervention with direct dual antithrombotic effects.
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The findings for ALA are mechanistically supported by effects of ALA on thrombosis, inflammation, arrhythmia, and endothelial function.
“Mechanistically, these findings are supported by effects of ALA on thrombosis, inflammation, arrhythmia, and endothelial function.43–47”
From ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies (2016) · cites this paper as [43]
Higher brain levels of omega-3 PUFAs and their atherosclerotic plaque stabilizing, anti-venous thrombosis, anti-inflammatory, antiplatelet, and anticoagulant properties result in fewer risks for embolism and plaque rupture.
“Higher brain levels of omega 3 PUFAs and their atherosclerotic plaque stabilizing properties, as well as their anti-venous thrombosis, anti-inflammatory, antiplatelet, and anticoagulant properties, result in fewer risks for embolism and plaque rupture [20,[78][79][80].”
From Update on Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Health (2022) · cites this paper as [79]
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- Authors
- Holy, E. W., Forestier, M., Richter, E. K., Akhmedov, A., Leiber, F., Camici, G. G., Mocharla, P., Lüscher, T. F., Beer, J. H., & Tanner, F. C.
- Affiliations
- University of Zurich (CH)
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2011-08
- Volume
- 31
- Issue
- 8
- Pages
- 1772-1780
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2170221270
- Cited by
- 88
- References
- 40
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 10 · 2021: 8 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 6 · 2014: 8 · 2013: 10 · 2012: 10
- FWCI
- 8.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation (310030)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (113328, 127422, 130500, 3100-068118.02/1, 3200B0, 310030)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Keywords
- alpha-linolenic acid, dietary fatty acids, arterial thrombus formation, tissue factor expression, platelet activation, platelet aggregation, p38 MAPK, NF-κB, extracellular signal-regulated kinase, c-Jun N-terminal kinase, vascular smooth muscle cells, endothelial cells, antithrombotic activity
- MeSH terms
- Animals, Cardiotonic Agents, Carotid Arteries, Carotid Artery Thrombosis, Cells, Cultured, Humans, Male, Mice, Inbred C57BL, Platelet Aggregation, Thromboplastin, Tumor Necrosis Factor-alpha, Platelet Activation, Gene Expression, NF-kappa B, alpha-Linolenic Acid, Dietary Supplements, MAP Kinase Signaling System, Myocytes, Smooth Muscle, Endothelial Cells, p38 Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinase 5, Mice
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