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Immobility-associated thromboprotection is conserved across mammalian species from bear to human
Department of Cardiology, University Hospital, LMU Munich, 81377 Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, 80802 Munich, Germany.
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany; Omicera Diagnostics, 82152 Martinsried, Germany.
Department of Cardiology, University Hospital, LMU Munich, 81377 Munich, Germany.
Department of Cardiology, University Hospital, LMU Munich, 81377 Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, 80802 Munich, Germany.
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2023 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 380, no 6641, p. 178-187Article in journal (Refereed) Published
Abstract [en]

Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. We aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as the most substantially reduced protein. HSP47 down-regulation or ablation attenuated immune cell activation and neutrophil extracellular trap formation, contributing to thromboprotection in bears, SCI patients, and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE.

Place, publisher, year, edition, pages
American Association for the Advancement of Science (AAAS) , 2023. Vol. 380, no 6641, p. 178-187
National Category
Cardiology and Cardiovascular Disease
Identifiers
URN: urn:nbn:se:oru:diva-105529DOI: 10.1126/science.abo5044ISI: 000986061000013PubMedID: 37053338Scopus ID: 2-s2.0-85152454110OAI: oai:DiVA.org:oru-105529DiVA, id: diva2:1751080
Funder
Max Planck SocietySwedish Environmental Protection Agency, 403584255EU, Horizon 2020, 833440
Note

Funding agencies:

German Research Foundation (DFG) PE2704/2-1 PE2704/3-1

DZHK (German Center for Cardiovascular Research) 80JSC018P0078 80JSC019P0010 100378833 806 32 006

LMU Munich's Clinician scientist program in vascular medicine (PRIME)

LMU Munich's institutional Forderprogramm fur Forschung und Lehre (FuFoLe)

European Research Council (ERC) IFF 2020-26

Helmholtz Association

German Aerospace Centre (DLR)

National Aeronautics & Space Administration (NASA)

Faculty of Health at Witten/Herdecke University, Germany

British Heart Foundation FS/17/31/32848 SFB 1123

Norwegian Environment Agency TRR267

LMU Munich's Institutional Strategy LMU excellent

Available from: 2023-04-17 Created: 2023-04-17 Last updated: 2025-02-10Bibliographically approved

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Fröbert, Ole

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