Kindberg, Jonas
- Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences
- Norwegian Institute Nature Research
Research article2023Peer reviewedOpen access
Immobility-associated thromboprotection is conserved across mammalian species from bear to human
Thienel, Manuela; Mueller-Reif, Johannes B.; Zhang, Zhe; Ehreiser, Vincent; Huth, Judith; Shchurovska, Khrystyna; Kilani, Badr; Schweizer, Lisa; Geyer, Philipp E.; Zwiebel, Maximilian; Novotny, Julia; Luesebrink, Enzo; Little, Gemma; Orban, Martin; Nicolai, Leo; El Nemr, Shaza; Titova, Anna; Spannagl, Michael; Kindberg, Jonas; Evans, Alina L.;
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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.
Published in
Science
2023, Volume: 380, number: 6641, pages: 178-187
SLU Authors
UKÄ Subject classification
Zoology
Immunology in the medical area
Publication identifier
DOI: https://doi.org/10.1126/science.abo5044
Permanent link to this page (URI)
https://res.slu.se/id/publ/121998