ArticleJournal of thrombosis and haemostasis : JTH2021
DHA 12-LOX-derived oxylipins regulate platelet activation and thrombus formation through a PKA-dependent signaling pathway.
Article in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- Supplementation with omega-3 or omega-6 fatty acids attenuates platelet reactivity in postmenopausal women.Clinical and translational science · 2022Trial
- Camellia diacylglycerol oil attenuates atherosclerosis and NAFLD by modulating gut microbiota and lipid metabolism in ApoEJournal of the science of food and agriculture · 2026Article
- VLX-1005, but not argatroban, prevents ITAM-mediated platelet activation and heparin-induced thrombocytopenia.Blood vessels, thrombosis & hemostasis · 2026Article
- Novel histone deacetylase inhibitor, CS014, attenuates in vivo thrombosis while maintaining hemostasis.Journal of thrombosis and haemostasis : JTH · 2026Article
- The mediating effect of DHA-mediated MPV improvement on coronary artery stenosis and its prognostic value.Frontiers in cardiovascular medicine · 2026Article
- Navigating the Effects of Anti-Atherosclerotic Supplements and Acknowledging Associated Bleeding Risks.International journal of molecular sciences · 2025Review
- Dysregulation of Arachidonic Acid Metabolism Drives Inflammatory Lipid Production in Localized Provoked Vulvodynia.Nutrients · 2025Article
- Role of annexin A7 in the occurrence and progression of coronary atherosclerosis: a narrative review.Cardiovascular diagnosis and therapy · 2025Review
- The EPA oxylipin, 12-HEPE, directly regulates human platelet activity.Journal of lipid research · 2025Article
- Docosahexaenoic acid mitigates experimental autoimmune prostatitis by inhibiting Th17 cell differentiation via the PPARγ/NF-κB/IL-17A pathway.Clinical and experimental immunology · 2025Article
- Observational Analyses of Ex Vivo Native American Platelet Responses.International journal of molecular sciences · 2024Observational
- Functional Foods in Preventing Human Blood Platelet Hyperactivity-Mediated Diseases-An Updated Review.Nutrients · 2024Review
- Ellagic acid-enhanced biocompatibility and bioactivity in multilayer core-shell gold nanoparticles for ameliorating myocardial infarction injury.Journal of nanobiotechnology · 2024Article
- Article
- Loss of 12-Lipoxygenase Improves the Post-Transfusion Function of Stored Platelets.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Investigating the catalytic efficiency of C22-Fatty acids with LOX human isozymes and the platelet response of the C22-oxylipin products.Archives of biochemistry and biophysics · 2023Article
- The Anti-Aggregative Potential of Resolvin E1 on Human Platelets.Molecules (Basel, Switzerland) · 2023Article
- Bioactive lipid regulation of platelet function, hemostasis, and thrombosis.Pharmacology & therapeutics · 2023Review
- Hydroperoxidation of Docosahexaenoic Acid by Human ALOX12 and pigALOX15-mini-LOX.International journal of molecular sciences · 2023Article
- Experimental venous thrombus resolution is driven by IL-6 mediated monocyte actions.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe effects of docosahexaenoic acid (DHA) on cardiovascular disease are controversial and a mechanistic understanding of how this omega-3 polyunsaturated fatty acid (ω-3 PUFA) regulates platelet reactivity and the subsequent risk of a thrombotic event is warranted. In platelets, DHA is oxidized by 12-lipoxygenase (12-LOX) producing the oxidized lipids (oxylipins) 11-HDHA and 14-HDHA. We hypothesized that 12-LOX DHA-oxylipins may be involved in the beneficial effects observed in dietary supplemental treatment with ω-3 PUFAs or DHA itself.
objectivesTo determine the effects of DHA, 11-HDHA, and 14-HDHA on platelet function and thrombus formation, and to elucidate the mechanism by which these ω-3 PUFAs regulate platelet activation. METHODS AND
resultsDHA, 11-HDHA, and 14-HDHA attenuated collagen-induced human platelet aggregation, but only the oxylipins inhibited ⍺IIbβ3 activation and decreased ⍺-granule secretion. Furthermore, treatment of whole blood with DHA and its oxylipins impaired platelet adhesion and accumulation to a collagen-coated surface. Interestingly, thrombus formation was only diminished in mice treated with 11-HDHA or 14-HDHA, and mouse platelet activation was inhibited following acute treatment with these oxylipins or chronic treatment with DHA, suggesting that under physiologic conditions, the effects of DHA are mediated through its oxylipins. Finally, the protective mechanism of DHA oxylipins was shown to be mediated via activation of protein kinase A.
conclusionsThis study provides the first mechanistic evidence of how DHA and its 12-LOX oxylipins inhibit platelet activity and thrombus formation. These findings support the beneficial effects of DHA as therapeutic intervention in atherothrombotic diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.