ArticleJournal of thrombosis and haemostasis : JTH2010
Non-genomic effects of PPARgamma ligands: inhibition of GPVI-stimulated platelet activation.
Article in Journal of thrombosis and haemostasis : JTH, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- Review
- Non-canonical non-genomic morphogen signaling in anucleate platelets: a critical determinant of prothrombotic function in circulation.Cell communication and signaling : CCS · 2024Review
- Emerging roles of lysophosphatidic acid receptor subtype 5 (LPAR5) in inflammatory diseases and cancer.Pharmacology & therapeutics · 2023Review
- Fatty acids negatively regulate platelet function through formation of noncanonical 15-lipoxygenase-derived eicosanoids.Pharmacology research & perspectives · 2023Article
- Transcription factors in megakaryocytes and platelets.Frontiers in immunology · 2023Review
- Plasma Concentration of Cortisol Negatively Associates with Platelet Reactivity in Older Subjects.International journal of molecular sciences · 2022Article
- Activation of Human Platelets byPathogens (Basel, Switzerland) · 2022Article
- Cucurbitacins Elicit Anti-Platelet Activity via Perturbation of the Cytoskeleton and Integrin Function.Thrombosis and haemostasis · 2022Article
- Critical role of peroxisome proliferator-activated receptor α in promoting platelet hyperreactivity and thrombosis under hyperlipidemia.Haematologica · 2022Article
- Review
- Zafirlukast is a broad-spectrum thiol isomerase inhibitor that inhibits thrombosis without altering bleeding times.British journal of pharmacology · 2021Article
- Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism.Frontiers in pharmacology · 2021Article
- Omega-6 DPA and its 12-lipoxygenase-oxidized lipids regulate platelet reactivity in a nongenomic PPARα-dependent manner.Blood advances · 2020Article
- A comparative pharmacogenomic analysis of three classic TCM prescriptions for coronary heart disease based on molecular network modeling.Acta pharmacologica Sinica · 2020Article
- Non-genomic effects of the Pregnane X Receptor negatively regulate platelet functions, thrombosis and haemostasis.Scientific reports · 2019Article
- Role of NF-κB in Platelet Function.International journal of molecular sciences · 2019Review
- A high-throughput chemical-genetics screen in murine adipocytes identifies insulin-regulatory pathways.The Journal of biological chemistry · 2019Article
- Cobimetinib and trametinib inhibit platelet MEK but do not cause platelet dysfunction.Platelets · 2019Article
- The HIV protease inhibitor, ritonavir, dysregulates human platelet function in vitro.Thrombosis research · 2018Article
- Non-genomic effects of nuclear receptors: insights from the anucleate platelet.Cardiovascular research · 2018Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPeroxisome proliferator-activated receptor-(gamma) (PPAR(gamma)) is expressed in human platelets although in the absence of genomic regulation in these cells, its functions are unclear.
objectiveIn the present study, we aimed to demonstrate the ability of PPAR(gamma) ligands to modulate collagen-stimulated platelet function and suppress activation of the glycoprotein VI (GPVI) signaling pathway.
methodsWashed platelets were stimulated with PPAR(gamma) ligands in the presence and absence of PPAR(gamma) antagonist GW9662 and collagen-induced aggregation was measured using optical aggregometry. Calcium levels were measured by spectrofluorimetry in Fura-2AM-loaded platelets and tyrosine phosphorylation levels of receptor-proximal components of the GPVI signaling pathway were measured using immunoblot analysis. The role of PPAR(gamma) agonists in thrombus formation was assessed using an in vitro model of thrombus formation under arterial flow conditions.
resultsPPAR(gamma) ligands inhibited collagen-stimulated platelet aggregation that was accompanied by a reduction in intracellular calcium mobilization and P-selectin exposure. PPAR(gamma) ligands inhibited thrombus formation under arterial flow conditions. The incorporation of GW9662 reversed the inhibitory actions of PPAR(gamma) agonists, implicating PPAR(gamma) in the effects observed. Furthermore, PPAR(gamma) ligands were found to inhibit tyrosine phosphorylation levels of multiple components of the GPVI signaling pathway. PPAR(gamma) was found to associate with Syk and LAT after platelet activation. This association was prevented by PPAR(gamma) agonists, indicating a potential mechanism for PPAR(gamma) function in collagen-stimulated platelet activation.
conclusionsPPAR(gamma) agonists inhibit the activation of collagen-stimulation of platelet function through modulation of early GPVI signalling.
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