ArticleBlood2011
The kinetics of αIIbβ3 activation determines the size and stability of thrombi in mice: implications for antiplatelet therapy.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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.
The trial behind it
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
43 citing papers in PubMed, 77 citations in OpenAlex.
- Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding.The Journal of experimental medicine · 2014Trial
- A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation.Blood · 2026Article
- Article
- Loss of 12-Lipoxygenase Improves the Post-Transfusion Function of Stored Platelets.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Reversible Platelet Integrin αIIbβ3 Activation and Thrombus Instability.International journal of molecular sciences · 2022Review
- Sanguinarine Attenuates Collagen-Induced Platelet Activation and Thrombus Formation.Biomedicines · 2021Article
- Injury measurements improve interpretation of thrombus formation data in the cremaster arteriole laser-induced injury model of thrombosis.Journal of thrombosis and haemostasis : JTH · 2020Article
- Novel Mouse Model for Studying Hemostatic Function of Human Platelets.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Subcellular localization of Rap1 GTPase activator CalDAG-GEFI is orchestrated by interaction of its atypical C1 domain with membrane phosphoinositides.Journal of thrombosis and haemostasis : JTH · 2020Article
- RasGRP2 Structure, Function and Genetic Variants in Platelet Pathophysiology.International journal of molecular sciences · 2020Review
- RAP GTPases and platelet integrin signaling.Platelets · 2019Review
- Article
- Calcium-induced structural rearrangements release autoinhibition in the Rap-GEF CalDAG-GEFI.The Journal of biological chemistry · 2018Article
- Platelet Signaling Pathways and New Inhibitors.Arteriosclerosis, thrombosis, and vascular biology · 2018Review
- Negative regulators of platelet activation and adhesion.Journal of thrombosis and haemostasis : JTH · 2018Review
- Marked bleeding diathesis in patients with platelet dysfunction due to a novel mutation in RASGRP2, encoding CalDAG-GEFI (p.Gly305Asp).Platelets · 2018Article
- Biology of Platelet Purinergic Receptors and Implications for Platelet Heterogeneity.Frontiers in pharmacology · 2018Review
- Phenotype analysis and clinical management in a large family with a novel truncating mutation inResearch and practice in thrombosis and haemostasis · 2017Article
- Hierarchical organization of the hemostatic response to penetrating injuries in the mouse macrovasculature.Journal of thrombosis and haemostasis : JTH · 2017Article
- Regulation of Platelet Activation and Coagulation and Its Role in Vascular Injury and Arterial Thrombosis.Interventional cardiology clinics · 2017Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Two major pathways contribute to Ras-proximate-1-mediated integrin activation in stimulated platelets. Calcium and diacyglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI, RasGRP2) mediates the rapid but reversible activation of integrin αIIbβ3, while the adenosine diphosphate receptor P2Y12, the target for antiplatelet drugs like clopidogrel, facilitates delayed but sustained integrin activation. To establish CalDAG-GEFI as a target for antiplatelet therapy, we compared how each pathway contributes to thrombosis and hemostasis in mice. Ex vivo, thrombus formation at arterial or venous shear rates was markedly reduced in CalDAG-GEFI(-/-) blood, even in the presence of exogenous adenosine diphosphate and thromboxane A(2). In vivo, thrombosis was virtually abolished in arterioles and arteries of CalDAG-GEFI(-/-) mice, while small, hemostatically active thrombi formed in venules. Specific deletion of the C1-like domain of CalDAG-GEFI in circulating platelets also led to protection from thrombus formation at arterial flow conditions, while it only marginally increased blood loss in mice. In comparison, thrombi in the micro- and macrovasculature of clopidogrel-treated wild-type mice grew rapidly and frequently embolized but were hemostatically inactive. Together, these data suggest that inhibition of the catalytic or the C1 regulatory domain in CalDAG-GEFI will provide strong protection from athero-thrombotic complications while maintaining a better safety profile than P2Y12 inhibitors like clopidogrel.
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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.