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.
Downloads per month over past year
Date Deposited: | 22 Mar 2023 14:50 | Date item deposited into CentAUR |
---|
Last Modified: | 16 Aug 2024 03:12 | Date item last modified |
---|
1. F. Khan, T. Tritschler, S. R. Kahn, M. A. Rodger, Venous thromboembolism. Lancet 398, 64-77 (2021).
2. K. Stark, S. Massberg, Interplay between inflammation and thrombosis in cardiovascular pathology. Nat Rev Cardiol 18, 666-682 (2021).
3. M. L. von Bruhl et al., Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 209, 819-835 (2012).
4. B. Engelmann, S. Massberg, Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 13, 34-45 (2013).
5. L. N. Godat, L. Kobayashi, D. C. Chang, R. Coimbra, Can we ever stop worrying about venous thromboembolism after trauma? J Trauma Acute Care Surg 78, 475-480; discussion 480-471 (2015).
6. M. Giorgi Pierfranceschi et al., The short- and long-term risk of venous thromboembolism in patients with acute spinal cord injury: a prospective cohort study. Thromb Haemost 109, 34-38 (2013).
7. R. A. Maxwell et al., Routine prophylactic vena cava filtration is not indicated after acute spinal cord injury. J Trauma 52, 902-906 (2002).
8. O. Frobert, A. M. Frobert, J. Kindberg, J. M. Arnemo, M. T. Overgaard, The brown bear as a translational model for sedentary lifestyle-related diseases. J Intern Med 287, 263-270 (2020).
9. P. G. Jorgensen et al., Low cardiac output as physiological phenomenon in hibernating, free- ranging Scandinavian brown bears (Ursus arctos) - an observational study. Cardiovasc Ultrasound 12, 36 (2014).
10. A. U. Friedrich et al., Comparative coagulation studies in hibernating and summer-active black bears (Ursus americanus). Thromb Res 158, 16-18 (2017).
11. T. L. Iles, T. G. Laske, D. L. Garshelis, P. A. Iaizzo, Blood clotting behavior is innately modulated in Ursus americanus during early and late denning relative to summer months. J Exp Biol 220, 455-459 (2017).
12. M. J. Engbers, J. W. Blom, M. Cushman, F. R. Rosendaal, A. van Hylckama Vlieg, The contribution of immobility risk factors to the incidence of venous thrombosis in an older population. J Thromb Haemost 12, 290-296 (2014).
13. K. G. Welinder et al., Biochemical Foundations of Health and Energy Conservation in Hibernating Free-ranging Subadult Brown Bear Ursus arctos. J Biol Chem 291, 22509-22523 (2016).
14. J. C. Meijers, W. L. Tekelenburg, B. N. Bouma, R. M. Bertina, F. R. Rosendaal, High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med 342, 696-701 (2000).
15. M. Cushman, E. S. O'Meara, A. R. Folsom, S. R. Heckbert, Coagulation factors IX through XIII
and the risk of future venous thrombosis: the Longitudinal Investigation of Thromboembolism
Etiology. Blood 114, 2878-2883 (2009).
16. S. M. Bates, J. I. Weitz, Coagulation assays. Circulation 112, e53-60 (2005).
17. P. E. Geyer et al., Plasma Proteome Profiling to Assess Human Health and Disease. Cell Syst 2,
185-195 (2016).
18. B. Sahdo et al., Body temperature during hibernation is highly correlated with a decrease in
circulating innate immune cells in the brown bear (Ursus arctos): a common feature among
hibernators? Int J Med Sci 10, 508-514 (2013).
19. H. R. Bouma et al., Low body temperature governs the decline of circulating lymphocytes during
hibernation through sphingosine-1-phosphate. Proc Natl Acad Sci U S A 108, 2052-2057 (2011).
20. H. R. Bouma et al., Reduction of body temperature governs neutrophil retention in hibernating
and nonhibernating animals by margination. J Leukoc Biol 94, 431-437 (2013).
21. J. A. Coppinger et al., Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood 103, 2096-2104 (2004).
22. S. R. Piersma et al., Proteomics of the TRAP-induced platelet releasate. J Proteomics 72, 91-109 (2009).
23. J. B. Muller et al., The proteome landscape of the kingdoms of life. Nature 582, 592-596 (2020).
24. M. Heck, B. A. Neely, Proteomics in Non-model Organisms: A New Analytical Frontier. J
Proteome Res 19, 3595-3606 (2020).
25. M. Zeiler, M. Moser, M. Mann, Copy number analysis of the murine platelet proteome spanning
the complete abundance range. Mol Cell Proteomics 13, 3435-3445 (2014).
26. P. E. Geyer, L. M. Holdt, D. Teupser, M. Mann, Revisiting biomarker discovery by plasma
proteomics. Mol Syst Biol 13, 942 (2017).
27. S. Ito, K. Nagata, Roles of the endoplasmic reticulum-resident, collagen-specific molecular
chaperone Hsp47 in vertebrate cells and human disease. J Biol Chem 294, 2133-2141 (2019).
28. P. Sasikumar et al., The chaperone protein HSP47: a platelet collagen binding protein that
contributes to thrombosis and hemostasis. J Thromb Haemost 16, 946-959 (2018).
29. W. J. Kaiser, L. M. Holbrook, K. L. Tucker, R. G. Stanley, J. M. Gibbins, A functional proteomic
method for the enrichment of peripheral membrane proteins reveals the collagen binding protein Hsp47 is exposed on the surface of activated human platelets. J Proteome Res 8, 2903-2914 (2009).
30. T. Petzold et al., beta1 integrin-mediated signals are required for platelet granule secretion and hemostasis in mouse. Blood 122, 2723-2731 (2013).
31. S. Wu et al., Hsp47 Inhibitor Col003 Attenuates Collagen-Induced Platelet Activation and Cerebral Ischemic-Reperfusion Injury in Rats. Front Pharmacol 12, 792263 (2021).
32. M. Jimenez-Alcazar, N. Kim, T. A. Fuchs, Circulating Extracellular DNA: Cause or
Consequence of Thrombosis? Semin Thromb Hemost 43, 553-561 (2017).
33. P. Smith et al., Markers of neutrophil activation and neutrophil extracellular traps in diagnosing
patients with acute venous thromboembolism: A feasibility study based on two VTE cohorts.
PLoS One 17, e0270865 (2022).
34. J. A. Diaz et al., Plasma DNA is Elevated in Patients with Deep Vein Thrombosis. J Vasc Surg
Venous Lymphat Disord 1, (2013).
35. S. Ito et al., A small-molecule compound inhibits a collagen-specific molecular chaperone and
could represent a potential remedy for fibrosis. J Biol Chem 292, 20076-20085 (2017).
36. A. Carestia et al., Mediators and molecular pathways involved in the regulation of neutrophil
extracellular trap formation mediated by activated platelets. J Leukoc Biol 99, 153-162 (2016).
37. N. Maugeri et al., Activated platelets present high mobility group box 1 to neutrophils, inducing
autophagy and promoting the extrusion of neutrophil extracellular traps. J Thromb Haemost 12,
2074-2088 (2014).
38. P. Andre et al., Critical role for Syk in responses to vascular injury. Blood 118, 5000-5010
(2011).
39. L. M. Holbrook et al., Platelets release novel thiol isomerase enzymes which are recruited to the
cell surface following activation. Br J Haematol 148, 627-637 (2010).
40. P. A. Randazzo et al., The Arf GTPase-activating protein ASAP1 regulates the actin
cytoskeleton. Proc Natl Acad Sci U S A 97, 4011-4016 (2000).
41. S. M. Aunon-Chancellor, J. M. Pattarini, S. Moll, A. Sargsyan, Venous Thrombosis during
Spaceflight. N Engl J Med 382, 89-90 (2020).
42. U. Limper et al., The thrombotic risk of spaceflight: has a serious problem been overlooked for
more than half of a century? Eur Heart J 42, 97-100 (2021).
43. A. L. Evans et al., Capture, anesthesia, and disturbance of free-ranging brown bears (Ursus
arctos) during hibernation. PLoS One 7, e40520 (2012).
44. L. Sachs et al., Ex vivo anticoagulants affect human blood platelet biomechanics with implications for high-throughput functional mechanophenotyping. Commun Biol 5, 86 (2022).
45. J. Krabbe et al., Blood collection technique, anticoagulants and storing temperature have minor effects on the isolation of polymorphonuclear neutrophils. Sci Rep 10, 14646 (2020).
46. N. A. Kulak, G. Pichler, I. Paron, N. Nagaraj, M. Mann, Minimal, encapsulated proteomic- sample processing applied to copy-number estimation in eukaryotic cells. Nat Methods 11, 319- 324 (2014).
47. F. Meier et al., Online Parallel Accumulation-Serial Fragmentation (PASEF) with a Novel Trapped Ion Mobility Mass Spectrometer. Mol Cell Proteomics 17, 2534-2545 (2018).
48. P. Skowronek et al., Rapid and In-Depth Coverage of the (Phospho-)Proteome With Deep Libraries and Optimal Window Design for dia-PASEF. Mol Cell Proteomics 21, 100279 (2022).
49. V. Demichev, C. B. Messner, S. I. Vernardis, K. S. Lilley, M. Ralser, DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput. Nat Methods 17,
41-44 (2020).
50. J. B. Muller-Reif et al., A New Parallel High-Pressure Packing System Enables Rapid
Multiplexed Production of Capillary Columns. Mol Cell Proteomics 20, 100082 (2021).
51. J. Cox, M. Mann, MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol 26, 1367-1372 (2008).
52. C. Thalin et al., Quantification of citrullinated histones: Development of an improved assay to reliably quantify nucleosomal H3Cit in human plasma. J Thromb Haemost 18, 2732-2743 (2020).
53. A. Pavy-Le Traon, M. Heer, M. V. Narici, J. Rittweger, J. Vernikos, From space to Earth: advances in human physiology from 20 years of bed rest studies (1986-2006). Eur J Appl Physiol 101, 143-194 (2007).
54. S. Tyanova et al., The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat Methods 13, 731-740 (2016).
55. D. B. Bekker-Jensen et al., Rapid and site-specific deep phosphoproteome profiling by data- independent acquisition without the need for spectral libraries. Nat Commun 11, 787 (2020). University Staff: Request a correction | Centaur Editors: Update this record
|