Immobility-associated thromboprotection is conserved across mammalian species from bear to human
Thienel, M., Müller-Reif, J. B., Zhang, Z., Ehreiser, V., Huth, J., Shchurovska, K., Kilani, B., Schweizer, L., Geyer, P. E., Zweibel, M., Novotny, J., Lüsebrink, E., Little, G., Orban, M., Nicolai, L., El Nemr, S., Titova, A., Spannagl, M., Kindberg, J., Evans, A. L. et al, Mach, O., Vogel, M., Tiedt, S., Ormanns, S., Kessler, B., Dueck, A., Friebe, A., Godsk Jørgensen, P., Majzoub-Altweck, M., Blutke, A., Polzin, A., Stark, K., Kääb, S., Maier, D., Gibbins, J. M.  ORCID: https://orcid.org/0000-0002-0372-5352, Limper, U., Frobert, O., Mann, M., Massberg, S. and Petzold, T.
(2023)
Immobility-associated thromboprotection is conserved across mammalian species from bear to human.
Science, 380 (6641).
pp. 178-187.
ISSN 1095-9203
It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing. To link to this item DOI: 10.1126/science.abo5044 Abstract/SummaryVenous 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. Here 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 most substantially reduced protein. HSP47 downregulation or ablation attenuated immune cell activation and NET 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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| Date Deposited: | 22 Mar 2023 14:50 | Date item deposited into CentAUR |
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