Reduced platelet forces underlie impaired hemostasis in mouse models of MYH9-related disease.pdf (2.75 MB)
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Reduced platelet forces underlie impaired hemostasis in mouse models of MYH9-related disease

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posted on 03.06.2022, 15:15 by Juliane Baumann, Laura Sachs, Otto Oliver, Ingmar SchoenIngmar Schoen, Peter Nestler, Carlo Zaninetti, Martin KennyMartin Kenny, Ruth Kranz, Hendrik von Eysmondt, Johanna Rodriguez, Tilman Schäffer, Zoltan Nagy, Andreas Greinacher, Raghavendra Palankar, Markus Bender
MYH9-related disease patients with mutations in the contractile protein non-muscle myosin heavy chain IIA display, among others, macrothrombocytopenia and a mild to moderate bleeding tendency. In this study, we used three mouse lines, each with one point mutation in the Myh9 gene at positions 702, 1424, or 1841, to investigate mechanisms underlying the increased bleeding risk. Agonist-induced activation of Myh9 mutant platelets was comparable to controls. However, myosin light chain phosphorylation after activation was reduced in mutant platelets, which displayed altered biophysical characteristics and generated lower adhesion, interaction, and traction forces. Treatment with tranexamic acid restored clot retraction and reduced bleeding. We verified our findings from the mutant mice with platelets from patients with the respective mutation. These data suggest that reduced platelet forces lead to an increased bleeding tendency in MYH9 -related disease patients, and treatment with tranexamic acid can improve the hemostatic function.

Teaser

Impaired hemostasis in Myh9 mutant mice due to reduced platelet forces can be improved by tranexamic acid.

Funding

TR240 grant with project number 374031971 of the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation)

Deutsches Zentrum für Herz-Kreislauf-Forschung (Postdoc start-up grant under grant agreement 81X3400107)

Bundesministerium für Bildung und Forschung (ZIK grant under grant agreement 03Z22CN11)

Royal College of Surgeons in Ireland

History

Comments

The original article is available at https://www.biorxiv.org/content Published version is available in Science advances https://doi.org/10.1126/sciadv.abn2627 & RCSI repository https://hdl.handle.net/10779/rcsi.19950428.v1

Published Citation

Baumann J. et al. Reduced platelet forces underlie impaired hemostasis in mouse models of MYH9-related disease. bioRxiv 2021

Publication Date

10 November 2021

PubMed ID

35584211

Department/Unit

  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Vascular Biology
  • Biomaterials and Regenerative Medicine

Publisher

Cold Spring Harbor Laboratory

Version

  • Submitted Version (Preprint)