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

[thumbnail of Acccepted abo5044_CombinedPDF_v4.pdf]
Preview
Text - Accepted Version
· Please see our End User Agreement before downloading.
| Preview

Please see our End User Agreement.

It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

Add to AnyAdd to TwitterAdd to FacebookAdd to LinkedinAdd to PinterestAdd to Email

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.

Altmetric Badge

Item Type Article
URI https://reading-clone.eprints-hosting.org/id/eprint/111253
Identification Number/DOI 10.1126/science.abo5044
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
Download/View statistics View download statistics for this item

Downloads

Downloads per month over past year

University Staff: Request a correction | Centaur Editors: Update this record

Search Google Scholar