Asymmetrical Forces Dictate the Distribution and Morphology of Platelets in Blood Clots.

Autor: Kovalenko TA; Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya str., 109029 Moscow, Russia., Giraud MN; Cardiology, Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland., Eckly A; BPPS UMR-S 1255, EFS Grand Est, FMTS, INSERM, University of Strasbourg, F-67065 Strasbourg, France., Ribba AS; Institute for Advanced Biosciences, University Grenoble Alpes, CNRS UMR 5309, INSERM U1209, F-38700 Grenoble, France., Proamer F; BPPS UMR-S 1255, EFS Grand Est, FMTS, INSERM, University of Strasbourg, F-67065 Strasbourg, France., Fraboulet S; Institute for Advanced Biosciences, University Grenoble Alpes, CNRS UMR 5309, INSERM U1209, F-38700 Grenoble, France., Podoplelova NA; Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya str., 109029 Moscow, Russia.; National Medical Research Centre of Pediatric Hematology, Oncology and Immunology Named after Dmitry Rogachev, 1 Samory Mashela St, 117198 Moscow, Russia., Valentin J; Cardiology, Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland., Panteleev MA; Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya str., 109029 Moscow, Russia.; National Medical Research Centre of Pediatric Hematology, Oncology and Immunology Named after Dmitry Rogachev, 1 Samory Mashela St, 117198 Moscow, Russia., Gonelle-Gispert C; Surgical Research Unit, Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland., Cook S; Cardiology, Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland., Lafanechère L; Institute for Advanced Biosciences, University Grenoble Alpes, CNRS UMR 5309, INSERM U1209, F-38700 Grenoble, France., Sveshnikova AN; Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya str., 109029 Moscow, Russia.; National Medical Research Centre of Pediatric Hematology, Oncology and Immunology Named after Dmitry Rogachev, 1 Samory Mashela St, 117198 Moscow, Russia., Sadoul K; Institute for Advanced Biosciences, University Grenoble Alpes, CNRS UMR 5309, INSERM U1209, F-38700 Grenoble, France.
Jazyk: angličtina
Zdroj: Cells [Cells] 2021 Mar 06; Vol. 10 (3). Date of Electronic Publication: 2021 Mar 06.
DOI: 10.3390/cells10030584
Abstrakt: Primary hemostasis consists in the activation of platelets, which spread on the exposed extracellular matrix at the injured vessel surface. Secondary hemostasis, the coagulation cascade, generates a fibrin clot in which activated platelets and other blood cells get trapped. Active platelet-dependent clot retraction reduces the clot volume by extruding the serum. Thus, the clot architecture changes with time of contraction, which may have an important impact on the healing process and the dissolution of the clot, but the precise physiological role of clot retraction is still not completely understood. Since platelets are the only actors to develop force for the retraction of the clot, their distribution within the clot should influence the final clot architecture. We analyzed platelet distributions in intracoronary thrombi and observed that platelets and fibrin co-accumulate in the periphery of retracting clots in vivo. A computational mechanical model suggests that asymmetric forces are responsible for a different contractile behavior of platelets in the periphery versus the clot center, which in turn leads to an uneven distribution of platelets and fibrin fibers within the clot. We developed an in vitro clot retraction assay that reproduces the in vivo observations and follows the prediction of the computational model. Our findings suggest a new active role of platelet contraction in forming a tight fibrin- and platelet-rich boundary layer on the free surface of fibrin clots.
Databáze: MEDLINE
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