A study that included hibernating brown bears – which rarely suffer from blood clots in their veins despite 6 months of immobilization during hibernation – has revealed a factor that appears to protect the animals against this immobility-associated thrombosis. The analysis, which also involved chronically immobile humans, points to reduced expression of platelet protein HSP47 as protective. The findings, also supported by research in pigs and mice, suggest that HSP47-associtated thromboprotection is conserved across several mammalian species and could be used to develop new antithrombotic therapeutics. Venous thromboembolism (VTE) – a cardiovascular condition that occurs when a blood clot forms in a vein – can result in death or severe disability. Those who experience short-term immobility due to illness or injury are at increased risk of developing VTE, while, paradoxically, chronically paralyzed individuals with spinal cord injuries do not have increased VTE risk. Looking beyond humans, hibernating brown bears – which remain immobile for months at a time – also do not appear to be at an increased risk for immobility-associated thrombosis during winter hibernation episodes. These observations suggest an underlying molecular mechanism that protects against thromboinflammation during long periods of immobilization in both species.
To better understand this thromboprotection, Manuela Thienel and colleagues evaluated blood from free-ranging brown bears during hibernation as well as from humans experiencing chronic immobilization. Using mass spectrometry-based proteomics, Thienel et al. discovered that platelets from hibernating bears, compared to the platelets of active brown bears, exhibit an antithrombotic signature characterized by decreased expression of heat shock protein 47 (HSP75) and reduced biomarkers of thromboinflammation. A similar pattern was observed in chronically immobilized humans as compared to their active counterparts, with findings further backed up in pigs and mice. To study the effect of immobilization in a physiological setting, the authors consigned a group of healthy individuals to bed rest immobilization and found that HSP47 became drastically reduced after 27 days. The findings indicate that HSP47 down-regulation due to chronic or long-term immobilization conveys protection from VTE by reversing the pro-thromboinflammatory state that normally follows immobilization. "The study by Thienel et al. shows that looking at nature is a good way to learn about human biology," writes Mirta Schattner in a related Perspective.
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