ArticleArteriosclerosis, thrombosis, and vascular biology2020
Pharmacological Blockade of Glycoprotein VI Promotes Thrombus Disaggregation in the Absence of Thrombin.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2020. 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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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
35 citing papers in PubMed, 71 citations in OpenAlex.
- Platelet-Collagen Interactions in Hemostatic Mechanisms.Advanced healthcare materials · 2026Review
- Platelet FcγRIIA is dispensable for hemostasis and arterial thrombosis in the absence of FcγRIIA-specific extracellular stimuli.Research and practice in thrombosis and haemostasis · 2026Article
- Regulation of platelet contractility by agonists present across a thrombus.Blood advances · 2026Article
- Research advances on platelet glycoprotein VI in ischemic stroke.Thrombosis journal · 2026Review
- Thrombin activity confinement and dense granule release drive the dynamics of arterial thrombus.PLoS computational biology · 2026Article
- Platelets and diseases: signal transduction and advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- GPVI-mediated thrombus stabilization of shear-induced platelet aggregates in a microfluidic stenosis.Biophysical journal · 2025Article
- GPVI inhibition: Advancing antithrombotic therapy in cardiovascular disease.European heart journal. Cardiovascular pharmacotherapy · 2024Review
- Platelet Activation Pathways Controlling Reversible Integrin αIIbβ3 Activation.TH open : companion journal to thrombosis and haemostasis · 2024Article
- Force balance ratio is a robust predictor of arterial thrombus stability.Biophysical journal · 2024Article
- Amentoflavone for treating cardiocerebrovascular diseases and neurological disorders.Frontiers in pharmacology · 2024Review
- Impact of antiplatelet therapy on microvascular thrombosis during ST-elevation myocardial infarction.Frontiers in molecular biosciences · 2024Review
- Platelet Receptor Glycoprotein VI-Dimer Is Overexpressed in Patients with Atrial Fibrillation at High Risk of Ischemic Stroke.TH open : companion journal to thrombosis and haemostasis · 2023Article
- Protease-activated receptors and glycoprotein VI cooperatively drive the platelet component in thromboelastography.Journal of thrombosis and haemostasis : JTH · 2023Article
- The relative importance of platelet integrins in hemostasis, thrombosis and beyond.Haematologica · 2023Review
- Targeting platelet GPVI with glenzocimab: a novel mechanism for inhibition.Blood advances · 2023Article
- The Btk inhibitor AB-95-LH34 potently inhibits atherosclerotic plaque-induced thrombus formation and platelet procoagulant activity.Journal of thrombosis and haemostasis : JTH · 2022Article
- Immunothrombosis and the Role of Platelets in Venous Thromboembolic Diseases.International journal of molecular sciences · 2022Review
- Platelets and tyrosine kinase inhibitors: clinical features, mechanisms of action, and effects on physiology.American journal of physiology. Cell physiology · 2022Review
- Platelet Redox Imbalance in Hypercholesterolemia: A Big Problem for a Small Cell.International journal of molecular sciences · 2022Review
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Authors and funding
18 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAtherothrombosis occurs upon rupture of an atherosclerotic plaque and leads to the formation of a mural thrombus. Computational fluid dynamics and numerical models indicated that the mechanical stress applied to a thrombus increases dramatically as a thrombus grows, and that strong inter-platelet interactions are essential to maintain its stability. We investigated whether GPVI (glycoprotein VI)-mediated platelet activation helps to maintain thrombus stability by using real-time video-microscopy. Approach and Results: We showed that GPVI blockade with 2 distinct Fab fragments promoted efficient disaggregation of human thrombi preformed on collagen or on human atherosclerotic plaque material in the absence of thrombin. ACT017-induced disaggregation was achieved under arterial blood flow conditions, and its effect increased with wall shear rate. GPVI regulated platelet activation within a growing thrombus as evidenced by the loss in thrombus contraction when GPVI was blocked, and the absence of the disaggregating effect of an anti-GPVI agent when the thrombi were fully activated with soluble agonists. The GPVI-dependent thrombus stabilizing effect was further supported by the fact that inhibition of any of the 4 key immunoreceptor tyrosine-based motif signalling molecules, src-kinases, Syk, PI3Kβ, or phospholipase C, resulted in kinetics of thrombus disaggregation similar to ACT017. The absence of ACT017-induced disaggregation of thrombi from 2 afibrinogenemic patients suggests that the role of GPVI requires interaction with fibrinogen. Finally, platelet disaggregation of fibrin-rich thrombi was also promoted by ACT017 in combination with r-tPA (recombinant tissue plasminogen activator).
conclusionsThis work identifies an unrecognized role for GPVI in maintaining thrombus stability and suggests that targeting GPVI could dissolve platelet aggregates with a poor fibrin content.
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Registered trials
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.