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

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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., Zweibel, M., Novotny, J., Lüsebrink, E., Little, G., Orban, M., Nicolai, L., El Nemr, S., Titova, A., Spannagl, M., Kindberg, J., Evans, A. L., 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 id iconORCID: 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 doi: 10.1126/science.abo5044

Abstract/Summary

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. 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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Item Type Article
URI https://reading-clone.eprints-hosting.org/id/eprint/111253
Item Type Article
Refereed Yes
Divisions Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Life Sciences > School of Biological Sciences > Biomedical Sciences
Uncontrolled Keywords Thromboprotection, thrombosis, venous thromboembolism (VTE), heat shock protein 47, hibernation, platelets, neutrophils, spinal cord injury.
Publisher American Association for the Advancement of Science
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