ArticleJournal of lipid research2012
Investigations of human platelet-type 12-lipoxygenase: role of lipoxygenase products in platelet activation.
Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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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.
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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
64 citing papers in PubMed, 95 citations in OpenAlex.
- Supplementation with omega-3 or omega-6 fatty acids attenuates platelet reactivity in postmenopausal women.Clinical and translational science · 2022Trial
- Article
- 13-HODE and 13-HOTrE, Present in the Traditional Chinese Medicine Herbal Extract di gu pi, Selectively Inhibit Platelet Function.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025Review
- 12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction and Microthrombi After Subarachnoid Hemorrhage in Mice.Translational stroke research · 2025Article
- Plasma oxylipins in children with sickle cell disease: Associations with biomarkers of inflammation and endothelial activation.Prostaglandins, leukotrienes, and essential fatty acids · 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
- Deficiency in platelet 12-lipoxygenase exacerbates inflammation and disease severity during SARS-CoV-2 infection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Deducing formation routes of oxylipins by quantitative multiple heart-cutting achiral-chiral 2D-LC-MS.Journal of lipid research · 2024Article
- Targeting Rap1b signaling cascades with CDNF: Mitigating platelet activation, plasma oxylipins and reperfusion injury in stroke.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- 12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction and Microthrombi after Subarachnoid Hemorrhage in Mice.Research square · 2024Article
- Article
- Cryo-EM structures of human arachidonate 12S-lipoxygenase bound to endogenous and exogenous inhibitors.Blood · 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
- Bioactive lipid regulation of platelet function, hemostasis, and thrombosis.Pharmacology & therapeutics · 2023Review
- Potential Benefits of Omega-3 Polyunsaturated Fatty Acids (N3PUFAs) on Cardiovascular Health Associated with COVID-19: An Update for 2023.Metabolites · 2023Review
- Hydroperoxidation of Docosahexaenoic Acid by Human ALOX12 and pigALOX15-mini-LOX.International journal of molecular sciences · 2023Article
- Review
- Fatty acids negatively regulate platelet function through formation of noncanonical 15-lipoxygenase-derived eicosanoids.Pharmacology research & perspectives · 2023Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Human platelet-type 12-lipoxygenase (12-LOX) has recently been shown to play an important role in regulation of human platelet function by reacting with arachidonic acid (AA). However, a number of other fatty acids are present on the platelet surface that, when cleaved from the phospholipid, can be oxidized by 12-LOX. We sought to characterize the substrate specificity of 12-LOX against six essential fatty acids: AA, dihomo-γ-linolenic acid (DGLA), eicosapentaenoic acid (EPA), α-linolenic acid (ALA), eicosadienoic acid (EDA), and linoleic acid (LA). Three fatty acids were comparable substrates (AA, DGLA, and EPA), one was 5-fold slower (ALA), and two showed no reactivity with 12-LOX (EDA and LA). The bioactive lipid products resulting from 12-LOX oxidation of DGLA, 12-(S)-hydroperoxy-8Z,10E,14Z-eicosatrienoic acid [12(S)-HPETrE], and its reduced product, 12(S)-HETrE, resulted in significant attenuation of agonist-mediated platelet aggregation, granule secretion, αIIbβ3 activation, Rap1 activation, and clot retraction. Treatment with DGLA similarly inhibited PAR1-mediated platelet activation as well as platelet clot retraction. These observations are in surprising contrast to our recent work showing 12(S)-HETE is a prothrombotic bioactive lipid and support our hypothesis that the overall effect of 12-LOX oxidation of fatty acids in the platelet is dependent on the fatty acid substrates available at the platelet membrane.
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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.