Immobility-associated thromboprotection is conserved across mammalian species from bear to human

Manuela Thienel; Johannes B. Müller-Reif; Zhe Zhang; Vincent Ehreiser; Judith Huth; Khrystyna Shchurovska; Badr Kilani; Lisa Schweizer; Philipp E. Geyer; Maximilian Zwiebel; Julia Novotny; Enzo Lüsebrink; Gemma Little; Martin Orban; Leo Nicolai; Shaza El Nemr; Anna Titova; Michael Spannagl; Jonas Kindberg; Alina L. Evans; Orpheus Mach; Matthias Vogel; Steffen Tiedt; Steffen Ormanns; Barbara Kessler; Anne Dueck; Andrea Friebe; Peter Godsk Jørgensen; Monir Majzoub-Altweck; Andreas Blutke; Amin Polzin; Konstantin Stark; Stefan Kääb; Doris Maier; Jonathan M. Gibbins; Ulrich Limper; Ole Frobert; Matthias Mann; Steffen Massberg; Tobias Petzold

doi:10.1126/science.abo5044

Immobility-associated thromboprotection is conserved across mammalian species from bear to human

Manuela Thienel, Johannes B. Müller-Reif, Zhe Zhang, Vincent Ehreiser, Judith Huth, Khrystyna Shchurovska, Badr Kilani, Lisa Schweizer, Philipp E. Geyer, Maximilian Zwiebel, Julia Novotny, Enzo Lüsebrink, Gemma Little, Martin Orban, Leo Nicolai, Shaza El Nemr, Anna Titova, Michael Spannagl, Jonas Kindberg, Alina L. EvansOrpheus Mach, Matthias Vogel, Steffen Tiedt, Steffen Ormanns, Barbara Kessler, Anne Dueck, Andrea Friebe, Peter Godsk Jørgensen, Monir Majzoub-Altweck, Andreas Blutke, Amin Polzin, Konstantin Stark, Stefan Kääb, Doris Maier, Jonathan M. Gibbins, Ulrich Limper, Ole Frobert^*, Matthias Mann^*, Steffen Massberg^*, Tobias Petzold^*

^*Corresponding author for this work

Department of Clinical Medicine - SDCA-Steno Diabetes Center Aarhus

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

29 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Science
Volume	380
Issue	6641
Pages (from-to)	178-187
Number of pages	10
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.abo5044
Publication status	Published - Apr 2023

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Thienel, M., Müller-Reif, J. B., Zhang, Z., Ehreiser, V., Huth, J., Shchurovska, K., Kilani, B., Schweizer, L., Geyer, P. E., Zwiebel, M., Novotny, J., Lüsebrink, E., Little, G., Orban, M., Nicolai, L., El Nemr, S., Titova, A., Spannagl, M., Kindberg, J., ... Petzold, T. (2023). Immobility-associated thromboprotection is conserved across mammalian species from bear to human. Science, 380(6641), 178-187. https://doi.org/10.1126/science.abo5044

@article{0e570ef233f64aeda159fc19393ce14b,

title = "Immobility-associated thromboprotection is conserved across mammalian species from bear to human",

abstract = "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.",

author = "Manuela Thienel and M{\"u}ller-Reif, {Johannes B.} and Zhe Zhang and Vincent Ehreiser and Judith Huth and Khrystyna Shchurovska and Badr Kilani and Lisa Schweizer and Geyer, {Philipp E.} and Maximilian Zwiebel and Julia Novotny and Enzo L{\"u}sebrink and Gemma Little and Martin Orban and Leo Nicolai and {El Nemr}, Shaza and Anna Titova and Michael Spannagl and Jonas Kindberg and Evans, {Alina L.} and Orpheus Mach and Matthias Vogel and Steffen Tiedt and Steffen Ormanns and Barbara Kessler and Anne Dueck and Andrea Friebe and J{\o}rgensen, {Peter Godsk} and Monir Majzoub-Altweck and Andreas Blutke and Amin Polzin and Konstantin Stark and Stefan K{\"a}{\"a}b and Doris Maier and Gibbins, {Jonathan M.} and Ulrich Limper and Ole Frobert and Matthias Mann and Steffen Massberg and Tobias Petzold",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 The Authors, some rights reserved.",

year = "2023",

month = apr,

doi = "10.1126/science.abo5044",

language = "English",

volume = "380",

pages = "178--187",

journal = "Science",

issn = "0036-8075",

publisher = "AMER ASSOC ADVANCEMENT SCIENCE",

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Thienel, M, Müller-Reif, JB, Zhang, Z, Ehreiser, V, Huth, J, Shchurovska, K, Kilani, B, Schweizer, L, Geyer, PE, Zwiebel, M, Novotny, J, Lüsebrink, E, Little, G, Orban, M, Nicolai, L, El Nemr, S, Titova, A, Spannagl, M, Kindberg, J, Evans, AL, Mach, O, Vogel, M, Tiedt, S, Ormanns, S, Kessler, B, Dueck, A, Friebe, A, Jørgensen, PG, Majzoub-Altweck, M, Blutke, A, Polzin, A, Stark, K, Kääb, S, Maier, D, Gibbins, JM, Limper, U, Frobert, O, Mann, M, Massberg, S & Petzold, T 2023, 'Immobility-associated thromboprotection is conserved across mammalian species from bear to human', Science, vol. 380, no. 6641, pp. 178-187. https://doi.org/10.1126/science.abo5044

TY - JOUR

T1 - Immobility-associated thromboprotection is conserved across mammalian species from bear to human

AU - Thienel, Manuela

AU - Müller-Reif, Johannes B.

AU - Zhang, Zhe

AU - Ehreiser, Vincent

AU - Huth, Judith

AU - Shchurovska, Khrystyna

AU - Kilani, Badr

AU - Schweizer, Lisa

AU - Geyer, Philipp E.

AU - Zwiebel, Maximilian

AU - Novotny, Julia

AU - Lüsebrink, Enzo

AU - Little, Gemma

AU - Orban, Martin

AU - Nicolai, Leo

AU - El Nemr, Shaza

AU - Titova, Anna

AU - Spannagl, Michael

AU - Kindberg, Jonas

AU - Evans, Alina L.

AU - Mach, Orpheus

AU - Vogel, Matthias

AU - Tiedt, Steffen

AU - Ormanns, Steffen

AU - Kessler, Barbara

AU - Dueck, Anne

AU - Friebe, Andrea

AU - Jørgensen, Peter Godsk

AU - Majzoub-Altweck, Monir

AU - Blutke, Andreas

AU - Polzin, Amin

AU - Stark, Konstantin

AU - Kääb, Stefan

AU - Maier, Doris

AU - Gibbins, Jonathan M.

AU - Limper, Ulrich

AU - Frobert, Ole

AU - Mann, Matthias

AU - Massberg, Steffen

AU - Petzold, Tobias

PY - 2023/4

Y1 - 2023/4

N2 - 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.

AB - 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.

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U2 - 10.1126/science.abo5044

DO - 10.1126/science.abo5044

M3 - Journal article

C2 - 37053338

AN - SCOPUS:85152454110

SN - 0036-8075

VL - 380

SP - 178

EP - 187

JO - Science

JF - Science

IS - 6641

ER -

Immobility-associated thromboprotection is conserved across mammalian species from bear to human

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