ArticleBlood2021
The metabolic enzyme pyruvate kinase M2 regulates platelet function and arterial thrombosis.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- G6PD suppresses thrombopoiesis via interfering with TMOD3-mediated actin dynamics.EMBO reports · 2026Article
- Systemic metabolic dysfunction drives platelet-mediated inflammation, fibrogenesis, and hepatocarcinogenesis in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Adjunctive therapeutic strategy for in-stent thrombosis:RSC advances · 2026Article
- Dimeric PKM2 in chondrocytes impairs mitochondrial homeostasis in osteoarthritis.Cell death & disease · 2026Article
- [Advances in research on the mechanisms of reactive oxygen species in platelet activation and thrombosis].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- Candidate biomarkers to identify mesothelioma patients at risk of developing venous thromboembolism post-surgery.Scientific reports · 2026Article
- Pyruvate kinase M2 promotes venous thrombosis by enhancing SNAP23-mediated platelet exocytosis and consequent NETosis.Blood advances · 2026Article
- Physiological predictors of exercise-induced increases in circulating BDNF isoforms and net cerebral lactate exchange in healthy adults.Frontiers in physiology · 2026Article
- Association between platelet-to-lymphocyte ratio and 28-day all-cause mortality in patients with asymptomatic coronary artery disease: a cohort study.European journal of medical research · 2025Article
- Identification of salvianolic acid A as an ADP receptor-selective and Gq/IPChinese medicine · 2025Article
- Deleting ACC1 in platelets alters phospholipidome and reduces platelet activation and thrombosis in mice.Blood advances · 2025Article
- Metabolic pathways in deep vein thrombosis: a new frontier for therapeutic intervention.Blood · 2025Review
- Extract ofCurrent issues in molecular biology · 2025Article
- Platelets and diseases: signal transduction and advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- Perfluorinated compounds exposure and atherogenic risk characteristics in a high-fat diet condition: In vitro/in vivo models and population panel study.PNAS nexus · 2025Article
- Role of Liver Kinase 1B in Platelet Activation and Host Defense DuringInternational journal of molecular sciences · 2025Article
- IRAP Drives Ribosomal Degradation to Refuel Energy for Platelet Activation during Septic Thrombosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Emerging Targets, Novel Directions, and Innovative Approaches in Thrombosis Therapy.Aging and disease · 2025Review
- The predictive function of miR-122-5p and its action mechanism by regulating PKM2 in metabolic syndrome.BMC endocrine disorders · 2025Article
- PKM2 is a key factor to regulate neurogenesis and cognition by controlling lactate homeostasis.Stem cell reports · 2025Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Very little is known about the role of metabolic regulatory mechanisms in platelet activation and thrombosis. Dimeric pyruvate kinase M2 (PKM2) is a crucial regulator of aerobic glycolysis that facilitates the production of lactate and metabolic reprogramming. Herein, we report that limiting PKM2 dimer formation, using the small molecule inhibitor ML265, negatively regulates lactate production and glucose uptake in human and murine stimulated platelets. Furthermore, limiting PKM2 dimer formation reduced agonist-induced platelet activation, aggregation, clot retraction, and thrombus formation under arterial shear stress in vitro in both human and murine platelets. Mechanistically, limiting PKM2 dimerization downregulated phosphatidylinositol 3-kinase (PI3K)-mediated protein kinase B or serine/threonine-specific protein kinase (Akt)/glycogen synthase kinase 3 (GSK3) signaling in human and murine platelets. To provide further evidence for the role of PKM2 in platelet function, we generated a megakaryocyte or platelet-specific PKM2-/- mutant strain (PKM2fl/flPF4Cre+). Platelet-specific PKM2-deficient mice exhibited impaired agonist-induced platelet activation, aggregation, clot retraction, and PI3K-mediated Akt/GSK3 signaling and were less susceptible to arterial thrombosis in FeCl3 injury-induced carotid- and laser injury-induced mesenteric artery thrombosis models, without altering hemostasis. Wild-type mice treated with ML265 were less susceptible to arterial thrombosis with unaltered tail bleeding times. These findings reveal a major role for PKM2 in coordinating multiple aspects of platelet function, from metabolism to cellular signaling to thrombosis, and implicate PKM2 as a potential target for antithrombotic therapeutic intervention.
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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.