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

6 Citations (Scopus)


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 languageEnglish
JournalScience (New York, N.Y.)
Issue number6641
Pages (from-to)178-187
Number of pages10
Publication statusPublished - 14 Apr 2023


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