ArticleMolecular pharmacology2013
Protease-activated receptor (PAR) 1 and PAR4 differentially regulate factor V expression from human platelets.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 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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Who cites it
32 citing papers in PubMed, 73 citations in OpenAlex.
- Temporal phosphoproteomics reveals key regulators of procoagulant COAT platelet generation.Blood vessels, thrombosis & hemostasis · 2026Article
- From Blood to Therapy: The Revolutionary Application of Platelets in Cancer-Targeted Drug Delivery.Journal of functional biomaterials · 2025Review
- Elevated protease-activated receptor 4 (PAR4) gene expression in Alzheimer's disease predicts cognitive decline.Neurobiology of aging · 2024Article
- A mouse model of the protease-activated receptor 4 Pro310Leu variant has reduced platelet reactivity.Journal of thrombosis and haemostasis : JTH · 2024Article
- Discovery of Protease-Activated Receptor 4 (PAR4)-Tethered Ligand Antagonists Using Ultralarge Virtual Screening.ACS pharmacology & translational science · 2024Article
- Role of protease-activated receptor 4 in mouse models of acute and chronic kidney injury.American journal of physiology. Renal physiology · 2024Article
- Targeting PAR4 to Reduce Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- The predominant PAR4 variant in individuals of African ancestry worsens murine and human stroke outcomes.The Journal of clinical investigation · 2023Article
- Platelet-Derived Extracellular Vesicles in Arterial Thrombosis.Advances in experimental medicine and biology · 2023Article
- PAR4-Mediated PI3K/Akt and RhoA/ROCK Signaling Pathways Are Essential for Thrombin-Induced Morphological Changes in MEG-01 Cells.International journal of molecular sciences · 2022Article
- Role of Neurons and Glia Cells in Wound Healing as a Novel Perspective Considering Platelet as a Conventional Player.Molecular neurobiology · 2022Review
- Discovery and Optimization of a Novel Series of Competitive and Central Nervous System-Penetrant Protease-Activated Receptor 4 (PAR4) Inhibitors.ACS chemical neuroscience · 2021Article
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- Article
- Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis.International journal of molecular sciences · 2020Article
- Using PAR4 Inhibition as an Anti-Thrombotic Approach: Why, How, and When?International journal of molecular sciences · 2019Review
- Platelets: emerging facilitators of cellular crosstalk in rheumatoid arthritis.Nature reviews. Rheumatology · 2019Review
- The role of coagulation and platelets in colon cancer-associated thrombosis.American journal of physiology. Cell physiology · 2019Article
- Protease-activated receptor 4 activity promotes platelet granule release and platelet-leukocyte interactions.Platelets · 2019Article
- Protease activated receptor 4: a backup receptor or a dark horse as a target in antiplatelet therapy?Annals of translational medicine · 2018Article
Corrections and comments
- Erratum issuedHamm, Heidi [corrected to Hamm, Heidi E]
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
With the recent interest of protease-activated receptors (PAR) 1 and PAR4 as possible targets for the treatment of thrombotic disorders, we compared the efficacy of protease-activated receptor (PAR)1 and PAR4 in the generation of procoagulant phenotypes on platelet membranes. PAR4-activating peptide (AP)-stimulated platelets promoted thrombin generation in plasma up to 5 minutes earlier than PAR1-AP-stimulated platelets. PAR4-AP-mediated factor V (FV) association with the platelet surface was 1.6-fold greater than for PAR1-AP. Moreover, PAR4 stimulation resulted in a 3-fold greater release of microparticles, compared with PAR1 stimulation. More robust FV secretion and microparticle generation with PAR4-AP was attributable to stronger and more sustained phosphorylation of myosin light chain at serine 19 and threonine 18. Inhibition of Rho-kinase reduced PAR4-AP-mediated FV secretion and microparticle generation to PAR1-AP-mediated levels. Thrombin generation assays measuring prothrombinase complex activity demonstrated 1.5-fold higher peak thrombin levels on PAR4-AP-stimulated platelets, compared with PAR1-AP-stimulated platelets. Rho-kinase inhibition reduced PAR4-AP-mediated peak thrombin generation by 25% but had no significant effect on PAR1-AP-mediated thrombin generation. In conclusion, stimulation of PAR4 on platelets leads to faster and more robust thrombin generation, compared with PAR1 stimulation. The greater procoagulant potential is related to more efficient FV release from intracellular stores and microparticle production driven by stronger and more sustained myosin light chain phosphorylation. These data have implications about the role of PAR4 during hemostasis and are clinically relevant in light of recent efforts to develop PAR antagonists to treat thrombotic disorders.
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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.