دورية أكاديمية
Fibrin-glycoprotein VI interaction increases platelet procoagulant activity and impacts clot structure.
| العنوان: | Fibrin-glycoprotein VI interaction increases platelet procoagulant activity and impacts clot structure. |
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| المؤلفون: | Gauer JS; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom., Duval C; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom., Xu RG; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom., Macrae FL; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom., McPherson HR; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom., Tiede C; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom., Tomlinson D; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom., Watson SP; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom., Ariëns RAS; Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom. Electronic address: R.A.S.Ariens@leeds.ac.uk. |
| المصدر: | Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2023 Mar; Vol. 21 (3), pp. 667-681. Date of Electronic Publication: 2022 Dec 22. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 101170508 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7836 (Electronic) Linking ISSN: 15387836 NLM ISO Abbreviation: J Thromb Haemost Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : [New York] : Elsevier Original Publication: Oxford : Blackwell Pub. |
| مواضيع طبية MeSH: | Fibrin*/chemistry , Thrombosis*, Animals ; Mice ; Blood Platelets/metabolism ; Eptifibatide/pharmacology ; Platelet Membrane Glycoproteins/metabolism |
| مستخلص: | Background: The glycoprotein VI (GPVI) signaling pathway was previously reported to direct procoagulant platelet activity through collagen binding. However, the impact of GPVI-fibrin interaction on procoagulant platelet development and how it modulates the clot structure are unknown. Objectives: To determine the effect of GPVI-fibrin interaction on the platelet phenotype and its impact on the clot structure. Methods: Procoagulant platelets in platelet-rich plasma clots were determined by scanning electron microscopy (wild-type and GPVI-deficient murine samples) and confocal microscopy. Procoagulant platelet number, clot density, clot porosity, and clot retraction were determined in platelet-rich plasma or whole blood clots of healthy volunteers in the presence of tyrosine kinase inhibitors (PRT-060318, ibrutinib, and dasatinib) and eptifibatide. Results: GPVI-deficient clots showed a higher nonprocoagulant vs procoagulant platelet ratio than wild-type clots. The fiber density and the procoagulant platelet number decreased in the presence of Affimer proteins, inhibiting GPVI-fibrin(ogen) interaction and the tyrosine kinase inhibitors. The effect of GPVI signaling inhibitors on the procoagulant platelet number was exacerbated by eptifibatide. The tyrosine kinase inhibitors led to an increase in clot porosity; however, no differences were observed in the final clot weight, following clot retraction with the tyrosine kinase inhibitors, except for ibrutinib. In the presence of eptifibatide, clot retraction was impaired. Conclusion: Our findings showed that GPVI-fibrin interaction significantly contributes to the development of procoagulant platelets and that inhibition of GPVI signaling increases clot porosity. Clot contractibility was impaired by the integrin αIIbβ3 and Btk pathway inhibition. Thus, inhibition of GPVI-fibrin interactions can alleviate structural characteristics that contribute to a prothrombotic clot phenotype, having potential important implications for novel antithrombotic interventions. Competing Interests: Declaration of competing interest There are no competing interests to disclose. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: J Thromb Haemost. 2023 Mar;21(3):465-466. (PMID: 36858794) |
| معلومات مُعتمدة: | RG/18/11/34036 United Kingdom BHF_ British Heart Foundation; 215861/Z/19/Z United Kingdom WT_ Wellcome Trust; 204951/B/16/Z United Kingdom WT_ Wellcome Trust; 204951/Z/16/Z United Kingdom WT_ Wellcome Trust; CH/03/003/15571 United Kingdom BHF_ British Heart Foundation |
| فهرسة مساهمة: | Keywords: GPVI; clot structure; fibrin; procoagulant platelets; tyrosine kinase inhibitors |
| المشرفين على المادة: | NA8320J834 (Eptifibatide) 9001-31-4 (Fibrin) 0 (Platelet Membrane Glycoproteins) 0 (platelet membrane glycoprotein VI) |
| تواريخ الأحداث: | Date Created: 20230125 Date Completed: 20230308 Latest Revision: 20230315 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.jtha.2022.09.004 |
| PMID: | 36696196 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-7836 |
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| DOI: | 10.1016/j.jtha.2022.09.004 |