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

• 成果类型: Article
• 署名作者: 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.; Mach, Orpheus; Vogel, Matthias; Tiedt, Steffen; Ormanns, Steffen; Kessler, Barbara; Dueck, Anne; Friebe, Andrea; Jorgensen, Peter Godsk; Majzoub-Altweck, Monir; Blutke, Andreas; Polzin, Amin; Stark, Konstantin; Kaab, Stefan; Maier, Doris; Gibbins, Jonathan M.; Limper, Ulrich; Frobert, Ole; Mann, Matthias; Massberg, Steffen; Petzold, Tobias
• 署名单位: University of Munich; Munich Heart Alliance; German Centre for Cardiovascular Research; Max Planck Society; University of Reading; University of Munich; Norwegian Institute Nature Research; Inland Norway University of Applied Sciences; University of Munich; University of Munich; University of Munich; Technical University of Munich; University of Munich; Helmholtz Association; German Aerospace Centre (DLR); Witten Herdecke University; Orebro University; Aarhus University; Aarhus University; Aarhus University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8236
• DOI: 10.1126/science.abo5044
• 发表日期: 2023-04-13
• 页码: 178-187
• 关键词: body-temperature governs; venous thromboembolism; ursus-arctos; thrombosis; RISK; coagulation; neutrophils; hibernation; proteins; surface

摘要

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.