ArticleBlood advances2018
Dichloroacetate, an inhibitor of pyruvate dehydrogenase kinases, inhibits platelet aggregation and arterial thrombosis.
Article in Blood advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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.
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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
34 citing papers in PubMed, 64 citations in OpenAlex.
- 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
- Platelets and diseases: signal transduction and advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- Platelet Extracellular Vesicles as Natural Delivery Vehicles for Mitochondrial Dysfunction Therapy?ACS biomaterials science & engineering · 2025Review
- Emerging Targets, Novel Directions, and Innovative Approaches in Thrombosis Therapy.Aging and disease · 2025Review
- Single-Cell Data and Weighted Correlation Network Analysis Revealed the Regulatory Mechanisms of Macrophages in Carotid Plaques.Journal of immunology research · 2025Article
- Deletion of pyruvate dehydrogenase kinases reduces susceptibility to deep vein thrombosis in mice.Blood advances · 2024Article
- Neutrophil glucose flux as a therapeutic target in antiphospholipid syndrome.The Journal of clinical investigation · 2024Article
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Theranostic Fluorescent Probes.Chemical reviews · 2024Review
- Platelet Metabolic Profiling Reveals Glycolytic and 1-Carbon Metabolites Are Essential for GP VI-Stimulated Human Platelets-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Metabolic targeting of platelets to combat thrombosis: dawn of a new paradigm?Cardiovascular research · 2023Review
- Platelets of COVID-19 patients display mitochondrial dysfunction, oxidative stress, and energy metabolism failure compatible with cell death.Research and practice in thrombosis and haemostasis · 2023Article
- Mitochondrial pyruvate dehydrogenase kinases contribute to platelet function and thrombosis in mice by regulating aerobic glycolysis.Blood advances · 2023Article
- Cobalt-conjugated carbon quantum dots for in vivo monitoring of the pyruvate dehydrogenase kinase inhibitor drug dichloroacetic acid.Scientific reports · 2022Article
- Modulation of Glycoprotein VI and Its Downstream Signaling Pathways as an Antiplatelet Target.International journal of molecular sciences · 2022Review
- Isotopically nonstationaryMetabolic engineering · 2022Article
- Dichloroacetate inhibits the degeneration of decellularized cardiovascular implants.European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery · 2021Article
- CREG1 improves the capacity of the skeletal muscle response to exercise endurance via modulation of mitophagy.Autophagy · 2021Article
- Regulation of Key Antiplatelet Pathways by Bioactive Compounds with Minimal Bleeding Risk.International journal of molecular sciences · 2021Review
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7 authors at 1 institution in 1 country.
Funding
Abstract
Resting platelets rely on oxidative phosphorylation (OXPHOS) and aerobic glycolysis (conversion of glucose to lactate in the presence of oxygen) to generate adenosine triphosphate, whereas activated platelets exhibit a high level of aerobic glycolysis, suggesting the existence of metabolic flexibility in platelets. Mitochondrial pyruvate dehydrogenase kinases (PDK 1-4) play a pivotal role in metabolic flexibility by inhibiting pyruvate dehydrogenase complex. We determined whether metabolic reprogramming, diverting metabolism from aerobic glycolysis back to OXPHOS, would inhibit platelet function. PDKs activity in human and mouse platelets was inhibited with dichloroacetic acid (DCA), a potent inhibitor of all 4 forms of PDK. Human and mouse platelets pretreated with DCA exhibited decreased platelet aggregation to suboptimal doses of collagen, convulxin, thrombin, and adenosine diphosphate concomitant with decreased glucose uptake. Bioenergetics profile revealed that platelets pretreated with DCA exhibited decreased aerobic glycolysis in response to convulxin only. Furthermore, DCA inhibited ATP secretion, thromboxane A2 generation, and tyrosine phosphorylation of Syk and PLCγ2 in response to collagen or convulxin in human and mouse platelets (
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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.