ArticleBlood advances2020
Omega-6 DPA and its 12-lipoxygenase-oxidized lipids regulate platelet reactivity in a nongenomic PPARα-dependent manner.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Platelet dysfunction reversal with cold-stored vs room temperature-stored platelet transfusions.Blood · 2024Trial
- Supplementation with omega-3 or omega-6 fatty acids attenuates platelet reactivity in postmenopausal women.Clinical and translational science · 2022Trial
- Fenofibrate attenuates hyperhomocysteinemia-potentiated thrombosis by restoring platelet fatty acid β-oxidation.Redox biology · 2026Article
- VLX-1005, but not argatroban, prevents ITAM-mediated platelet activation and heparin-induced thrombocytopenia.Blood vessels, thrombosis & hemostasis · 2026Article
- Hemostasis-Sparing Antiplatelet Therapy: Current Concepts and Emerging Targets in Arterial Thrombosis.Biomolecules & therapeutics · 2026Review
- Profiling of lipid mediators and oxylipins in SARS-CoV-2 infection associated thrombosis.Scientific reports · 2025Article
- The EPA oxylipin, 12-HEPE, directly regulates human platelet activity.Journal of lipid research · 2025Article
- Multiple Roles of Palmitic Acid in Cardiovascular Diseases.Journal of inflammation research · 2025Review
- Identification of oxylipins and lipid mediators in pulmonary embolism.Lipids in health and disease · 2024Article
- Antiplatelet strategies: past, present, and future.Journal of thrombosis and haemostasis : JTH · 2023Review
- Biofilm-derived oxylipin 10-HOME-mediated immune response in women with breast implants.The Journal of clinical investigation · 2023Article
- Article
- 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
- Bioactive lipid regulation of platelet function, hemostasis, and thrombosis.Pharmacology & therapeutics · 2023Review
- Fatty acids negatively regulate platelet function through formation of noncanonical 15-lipoxygenase-derived eicosanoids.Pharmacology research & perspectives · 2023Article
- Critical role of peroxisome proliferator-activated receptor α in promoting platelet hyperreactivity and thrombosis under hyperlipidemia.Haematologica · 2022Article
- Eicosanoids in inflammation in the blood and the vessel.Frontiers in pharmacology · 2022Review
- Impact of Phytochemicals on PPAR Receptors: Implications for Disease Treatments.PPAR research · 2022Review
- Effects of Nutrients on Platelet Function: A Modifiable Link between Metabolic Syndrome and Neurodegeneration?Biomolecules · 2021Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Arterial thrombosis is the underlying cause for a number of cardiovascular-related events. Although dietary supplementation that includes polyunsaturated fatty acids (PUFAs) has been proposed to elicit cardiovascular protection, a mechanism for antithrombotic protection has not been well established. The current study sought to investigate whether an omega-6 essential fatty acid, docosapentaenoic acid (DPAn-6), and its oxidized lipid metabolites (oxylipins) provide direct cardiovascular protection through inhibition of platelet reactivity. Human and mouse blood and isolated platelets were treated with DPAn-6 and its 12-lipoxygenase (12-LOX)-derived oxylipins, 11-hydroxy-docosapentaenoic acid and 14-hydroxy-docosapentaenoic acid, to assess their ability to inhibit platelet activation. Pharmacological and genetic approaches were used to elucidate a role for DPA and its oxylipins in preventing platelet activation. DPAn-6 was found to be significantly increased in platelets following fatty acid supplementation, and it potently inhibited platelet activation through its 12-LOX-derived oxylipins. The inhibitory effects were selectively reversed through inhibition of the nuclear receptor peroxisome proliferator activator receptor-α (PPARα). PPARα binding was confirmed using a PPARα transcription reporter assay, as well as PPARα-/- mice. These approaches confirmed that selectivity of platelet inhibition was due to effects of DPA oxylipins acting through PPARα. Mice administered DPAn-6 or its oxylipins exhibited reduced thrombus formation following vessel injury, which was prevented in PPARα-/- mice. Hence, the current study demonstrates that DPAn-6 and its oxylipins potently and effectively inhibit platelet activation and thrombosis following a vascular injury. Platelet function is regulated, in part, through an oxylipin-induced PPARα-dependent manner, suggesting that targeting PPARα may represent an alternative strategy to treat thrombotic-related diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.