A thrombus is formed by a gradient of platelet activation and procoagulant endothelium.

Autor: Carminita E; Aix-Marseille University (AMU), Center for Cardiovascular and Nutrition research, (C2VN) 1263 INSERM, INRAE 1260, Marseille, France.; Plateforme Technologique Aix-Marseille, plateforme d'imagerie vasculaire et de microscopie intravitale (PIVMI), Marseille, France., Tourn J; Aix-Marseille University (AMU), Center for Cardiovascular and Nutrition research, (C2VN) 1263 INSERM, INRAE 1260, Marseille, France.; Plateforme Technologique Aix-Marseille, plateforme d'imagerie vasculaire et de microscopie intravitale (PIVMI), Marseille, France., Crescence L; Aix-Marseille University (AMU), Center for Cardiovascular and Nutrition research, (C2VN) 1263 INSERM, INRAE 1260, Marseille, France.; Plateforme Technologique Aix-Marseille, plateforme d'imagerie vasculaire et de microscopie intravitale (PIVMI), Marseille, France., Brouilly N; Aix-Marseille University, CNRS UMR 7288, Institut de Biologie du Développement de Marseille (IBDM), Marseille, France., Merrill-Skoloff G; Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA., Mazharian A; Université de Strasbourg, INSERM, Etablissement Français du Sang Grand-Est, Unité Mixte de Recherche-S 1255, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France., Dubois C; Aix-Marseille University (AMU), Center for Cardiovascular and Nutrition research, (C2VN) 1263 INSERM, INRAE 1260, Marseille, France.; Plateforme Technologique Aix-Marseille, plateforme d'imagerie vasculaire et de microscopie intravitale (PIVMI), Marseille, France., Panicot-Dubois L; Aix-Marseille University (AMU), Center for Cardiovascular and Nutrition research, (C2VN) 1263 INSERM, INRAE 1260, Marseille, France.; Plateforme Technologique Aix-Marseille, plateforme d'imagerie vasculaire et de microscopie intravitale (PIVMI), Marseille, France.
Jazyk: angličtina
Zdroj: Research and practice in thrombosis and haemostasis [Res Pract Thromb Haemost] 2023 Sep 21; Vol. 7 (7), pp. 102209. Date of Electronic Publication: 2023 Sep 21 (Print Publication: 2023).
DOI: 10.1016/j.rpth.2023.102209
Abstrakt: Background: The contribution of platelets in thrombosis within microcirculation has been extensively documented in the literature. We previously showed, in vivo , that platelet activation revealed by intracellular calcium mobilization was a crucial step in the growth of thrombi following laser-induced injury, a model of thromboinflammation.
Objective: Our goal was to investigate the extent of platelet activation and the spatial distribution of platelets throughout a growing thrombus.
Methods: We employed a multimodal, correlative microscopy approach and computational biology to study the state of platelets on a growing thrombus obtained after a laser injury.
Results: We observed a reversible intracellular platelet calcium mobilization that correlates with the time a platelet resides during thrombus growth. Our bioinformatics analysis displayed the following 3 distinct platelet subpopulations resident within a thrombus: (1) resting, (2) partially activated, and (3) "fully" activated platelets. The spatial distribution of the platelet subpopulations in the thrombus creates a double gradient in both the transversal and longitudinal axis, with the maximal percentage of fully activated platelets close to the site of injury. However, these activated platelets did not express negative phospholipids. The injured endothelium was identified to play a vital role in activating the blood coagulation cascade in this model of thrombosis.
Conclusion: Following a laser-induced injury, thrombi are formed by a gradient of activated platelets from the injury site to the periphery of the thrombus. These different activation states of platelets throughout the thrombi regulate the biomechanics of the thrombus. The injured endothelium, rather than platelets, was identified to play a key role in the activation of the blood coagulation cascade in this model of thromboinflammation.
(© 2023 The Authors.)
Databáze: MEDLINE
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