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

Thienel, Manuela; Müller-Reif, Johannes B.; Zhang, Zhe; Ehreiser, Vincent; Huth, Judith; Shchurovska, Khrystyna; Kilani, Badr; Schweizer, Lisa; Geyer, Philipp E.; Zwiebel, Maximilian; Novotny, Julia; Lüsebrink, Enzo; Little, Gemma; Orban, Mathias; Nicolai, Leo; Nemr, Shaza El; Titova, Anna; Spannagl, Michael; Kindberg, Jonas; Evans, Alina L.; Mach, Orpheus; Vogel, Matthias; Tiedt, Steffen; Ormanns, Steffen; Keßler, Barbara; Dueck, Anne; Friebe, Andrea; Jørgensen, Peter Godsk; Majzoub-Altweck, Monir; Blutke, Andreas; Polzin, Amin; Stark, Konstantin; Kääb, Stefan; Maier, Doris; Gibbins, Jonathan M.; Limper, Ulrich; Fröbert, Ole; Mann, Matthias; Maßberg, Steffen; Petzold, Tobias

doi:10.1126/science.abo5044

Cited by 30 publications

(28 citation statements)

References 56 publications

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“…Of potential further interest to the regulation of myosin would be the differential expression of heat shock proteins (HSPs) during hibernation. Various HSPs have been observed to be differentially expressed during hibernation in mammals such as bears and bats[61, 62]. This is of relevance to the data from our study as HSPs have been demonstrated to be able to bind sarcomeric proteins and regulate their turnover, including that of myosin itself [63, 64].…”

Section: Discussionsupporting

confidence: 75%

Remodelling of skeletal muscle myosin metabolic states in hibernating mammals

Lewis,

Melhedegaard,

Ognjanovic

et al. 2023

Preprint

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Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators,Ictidomys tridecemlineatusandEliomys quercinusand larger hibernators,Ursus arctosandUrsus americanus. We then conducted loaded Mant-ATP chase experiments alongside X-ray diffraction to measure resting myosin dynamics and its ATP demand. In parallel, we performed multiple proteomics analyses. Our results showed a preservation of myosin structure inU. arctosandU. americanusduring hibernation, whilst inI. tridecemlineatusandE. quercinus, changes in myosin metabolic states during torpor unexpectedly led to higher levels in energy expenditure of type II, fast-twitch muscle fibers at ambient lab temperatures (20°C). Upon repeating loaded Mant-ATP chase experiments at 8°C (near the body temperature of torpid animals), we found that myosin ATP consumption in type II muscle fibers was reduced by 77-107% during torpor compared to active periods. Additionally, we observed Myh2 hyper-phosphorylation during torpor inI. tridecemilineatus, which was predicted to stabilize the myosin molecule. This may act as a potential molecular mechanism mitigating myosin-associated increases in skeletal muscle energy expenditure during periods of torpor in response to cold exposure. Altogether, we demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes to the ATP consumption of skeletal muscle. Additionally, we observe that it is further altered in response to cold exposure and highlight myosin as a potentially contributor to skeletal muscle non-shivering thermogenesis.

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Section: Discussionsupporting

confidence: 75%

Remodelling of skeletal muscle myosin metabolic states in hibernating mammals

Lewis,

Melhedegaard,

Ognjanovic

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Of potential further interest to the regulation of myosin would be the differential expression of heat shock proteins (HSPs) during hibernation. Various HSPs have been observed to be differentially expressed during hibernation in mammals such as bears and bats ( Thienel et al, 2023 ; Lee et al, 2008 ). This is of relevance to the data from our study as HSPs have been demonstrated to be able to bind sarcomeric proteins and regulate their turnover, including that of myosin itself ( Glazier et al, 2018 ; Ojima et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Remodeling of skeletal muscle myosin metabolic states in hibernating mammals

Lewis,

Melhedegaard,

Ognjanovic

et al. 2024

eLife

Self Cite

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Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators, Ictidomys tridecemlineatus and Eliomys quercinus and larger hibernators, Ursus arctos and Ursus americanus . We then conducted loaded Mant-ATP chase experiments alongside X-ray diffraction to measure resting myosin dynamics and its ATP demand. In parallel, we performed multiple proteomics analyses. Our results showed a preservation of myosin structure in U. arctos and U. americanus during hibernation, whilst in I. tridecemlineatus and E. quercinus , changes in myosin metabolic states during torpor unexpectedly led to higher levels in energy expenditure of type II, fast-twitch muscle fibers at ambient lab temperatures (20°C). Upon repeating loaded Mant-ATP chase experiments at 8°C (near the body temperature of torpid animals), we found that myosin ATP consumption in type II muscle fibers was reduced by 77-107% during torpor compared to active periods. Additionally, we observed Myh2 hyper-phosphorylation during torpor in I. tridecemilineatus , which was predicted to stabilize the myosin molecule. This may act as a potential molecular mechanism mitigating myosin-associated increases in skeletal muscle energy expenditure during periods of torpor in response to cold exposure. Altogether, we demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes to the ATP consumption of skeletal muscle. Additionally, we observe that it is further altered in response to cold exposure and highlight myosin as a potentially contributor to skeletal muscle non-shivering thermogenesis.

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“…10,11,132 Increasing evidence supports an important role for platelets in venous thrombosis through various mechanisms. 133,134 Cross talk between platelets and monocytes seems to be important in the initiation and propagation of venous thromboembolism, partly mediated by induction of tissue factor expression on the surface of monocytes following platelet binding. 135,136 Plateletdependent generation of highly prothrombotic extracellular traps from neutrophils has also been implicated in the development of venous thrombosis.…”

Section: Platelets In Postinjury Thrombosismentioning

confidence: 99%

“…135,136 Plateletdependent generation of highly prothrombotic extracellular traps from neutrophils has also been implicated in the development of venous thrombosis. 134,137 Given that platelet-leukocyte interactions are frequent after major trauma, this may represent a mechanism of postinjury thrombosis that is not targeted by current prophylactic regimens.…”

Section: Platelets In Postinjury Thrombosismentioning

confidence: 99%

Platelets in Hemostasis, Thrombosis, and Inflammation After Major Trauma

Vulliamy,

Armstrong

2024

ATVB

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Trauma currently accounts for 10% of the total global burden of disease and over 5 million deaths per year, making it a leading cause of morbidity and mortality worldwide. Although recent advances in early resuscitation have improved early survival from critical injury, the mortality rate in patients with major hemorrhage approaches 50% even in mature trauma systems. A major determinant of clinical outcomes from a major injury is a complex, dynamic hemostatic landscape. Critically injured patients frequently present to the emergency department with an acute traumatic coagulopathy that increases mortality from bleeding, yet, within 48 to 72 hours after injury will switch from a hypocoagulable to a hypercoagulable state with increased risk of venous thromboembolism and multiple organ dysfunction. This review will focus on the role of platelets in these processes. As effectors of hemostasis and thrombosis, they are central to each phase of recovery from injury, and our understanding of postinjury platelet biology has dramatically advanced over the past decade. This review describes our current knowledge of the changes in platelet behavior that occur following major trauma, the mechanisms by which these changes develop, and the implications for clinical outcomes. Importantly, supported by research in other disease settings, this review also reflects the emerging role of thromboinflammation in trauma including cross talk between platelets, innate immune cells, and coagulation. We also address the unresolved questions and significant knowledge gaps that remain, and finally highlight areas that with the further study will help deliver further improvements in trauma care.

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

Cited by 30 publications

References 56 publications

Remodelling of skeletal muscle myosin metabolic states in hibernating mammals

Remodelling of skeletal muscle myosin metabolic states in hibernating mammals

Remodeling of skeletal muscle myosin metabolic states in hibernating mammals

Platelets in Hemostasis, Thrombosis, and Inflammation After Major Trauma

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