ArticleBlood2014
Platelet 12-LOX is essential for FcγRIIa-mediated platelet activation.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 91 citations in OpenAlex.
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- Novel histone deacetylase inhibitor, CS014, attenuates in vivo thrombosis while maintaining hemostasis.Journal of thrombosis and haemostasis : JTH · 2026Article
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- Translational immunothrombosis in autoimmune Heparin-Induced thrombocytopenia: targeting the FcγRIIa-Syk-BTK and complement pathways.Clinical and experimental medicine · 2026Review
- 13-HODE and 13-HOTrE, Present in the Traditional Chinese Medicine Herbal Extract di gu pi, Selectively Inhibit Platelet Function.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Immobilized IgG-containing immune complexes require platelets to recruit neutrophils during inflammation.The Journal of clinical investigation · 2026Article
- Regulatory roles of bioactive lipids in vascular homeostasis and remodeling.Medical review (2021) · 2026Review
- Platelet activation, aspirin, and cancer: From basic science to clinical trials.Pharmacological reviews · 2026Review
- The crucial role of thromboxane AFrontiers in pharmacology · 2026Review
- 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
- Beyond platelet activation: dysregulated lipid metabolism in defining risk and pathophysiology of VITT.Research and practice in thrombosis and haemostasis · 2025Article
- Structural and Functional Biology of Mammalian ALOX Isoforms with Particular Emphasis on Enzyme Dimerization and Their Allosteric Properties.International journal of molecular sciences · 2024Review
- P2Y12 Receptor Inhibitor for Antiaggregant Therapies: From Molecular Pathway to Clinical Application.International journal of molecular sciences · 2024Review
- Eugenol Suppresses Platelet Activation and Mitigates Pulmonary Thromboembolism in Humans and Murine Models.International journal of molecular sciences · 2024Article
- Ginkgetin effectively mitigates collagen and AA-induced platelet activation via PLCγ2 but not cyclic nucleotide-dependent pathway in human.Journal of cellular and molecular medicine · 2024Article
- Oxylipins as therapeutic indicators of herbal medicines in cardiovascular diseases: a review.Frontiers in pharmacology · 2024Review
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Platelets are essential in maintaining hemostasis following inflammation or injury to the vasculature. Dysregulated platelet activity often results in thrombotic complications leading to myocardial infarction and stroke. Activation of the FcγRIIa receptor leads to immune-mediated thrombosis, which is often life threatening in patients undergoing heparin-induced thrombocytopenia or sepsis. Inhibiting FcγRIIa-mediated activation in platelets has been shown to limit thrombosis and is the principal target for prevention of immune-mediated platelet activation. In this study, we show for the first time that platelet 12(S)-lipoxygenase (12-LOX), a highly expressed oxylipin-producing enzyme in the human platelet, is an essential component of FcγRIIa-mediated thrombosis. Pharmacologic inhibition of 12-LOX in human platelets resulted in significant attenuation of FcγRIIa-mediated aggregation. Platelet 12-LOX was shown to be essential for FcγRIIa-induced phospholipase Cγ2 activity leading to activation of calcium mobilization, Rap1 and protein kinase C activation, and subsequent activation of the integrin αIIbβ3. Additionally, platelets from transgenic mice expressing human FcγRIIa but deficient in platelet 12-LOX, failed to form normal platelet aggregates and exhibited deficiencies in Rap1 and αIIbβ3 activation. These results support an essential role for 12-LOX in regulating FcγRIIa-mediated platelet function and identifies 12-LOX as a potential therapeutic target to limit immune-mediated thrombosis.
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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.