Von Willebrand factor is reversibly decreased during torpor in 13-lined ground squirrels

Cooper, Scott; Sell, Shawn; Nelson, Luke; Hawes, Jennifer; Benrud, Jacob A.; Kohlnhofer, Bridget M.; Burmeister, Bradley R.; Flood, Veronica H.

doi:10.1007/s00360-015-0941-5

Cited by 16 publications

(16 citation statements)

References 54 publications

(83 reference statements)

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“…Many proteins known to be involved in platelet function did not show differential expression include the surface glycoprotein receptors (GPIBA, GPIBB, GPIIB, GPIIIB) and proteins found in secretory granules (vWF, P selectin). In contrast, expression of vWF mRNA by endothelial cells in the lung was lower during torpor, suggesting a different regulatory mechanism in megakaryocytes and endothelial cells during hibernation (21). Transcription of genes in megakaryocytes does not appear to be lower during hibernation in spite of a decrease in megakaryocyte numbers.…”

Section: Discussionmentioning

confidence: 81%

Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels

Cooper

Sell

Fahrenkrog

et al. 2016

Physiological Genomics

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M. Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels. Physiol Genomics 48: 513-525, 2016. First published May 20, 2016 doi:10.1152/physiolgenomics.00120.2015.-Mammalian hibernators adapt to prolonged periods of immobility, hypometabolism, hypothermia, and oxidative stress, each capable of reducing bone marrow activity. In this study bone marrow transcriptomes were compared among thirteen-lined ground squirrels collected in July, winter torpor, and winter interbout arousal (IBA). The results were consistent with a suppression of acquired immune responses, and a shift to innate immune responses during hibernation through higher complement expression. Consistent with the increase in adipocytes found in bone marrow of hibernators, expression of genes associated with white adipose tissue are higher during hibernation. Genes that should strengthen the bone by increasing extracellular matrix were higher during hibernation, especially the collagen genes. Finally, expression of heat shock proteins were lower, and cold-response genes were higher, during hibernation. No differential expression of hematopoietic genes involved in erythrocyte or megakaryocyte production was observed. This global view of the changes in the bone marrow transcriptome over both short term (torpor vs. IBA) and long term (torpor vs. July) hypothermia can explain several observations made about circulating blood cells and the structure and strength of the bone during hibernation. erythrocyte; leukocyte; megakaryocyte; osteoblast; adipose BONE MARROW IS A COMPLEX ORGAN consisting of many different cell types and stem cell pools. These cells express both unique and common sets of genes and likely influence each other's activities. Hematopoietic stem cells can differentiate into lymphoid progenitor cells that produce natural killer cells and lymphocytes, or into myeloid progenitor cells that give rise to erythrocytes, the remaining leukocytes, and megakaryocytes. Megakaryocytes in turn shed anucleated platelets involved in blood clotting and inflammation. Bone marrow resident mesenchymal stem cells can differentiate to produce resident bone cells including osteoblasts, adipocytes, and chondrocytes (64). Osteoblasts can terminally differentiate into osteocytes and are involved in maintaining bone strength and extracellular matrix production. Bone marrow adipose composition is affected by age, diet, and disease states. Bone marrow may also contain skeletal muscle and hepatocyte stem cell pools. Because of the rapid rate of mitosis by multiple resident stem cell pools, bone marrow is sensitive to damage by radiation and chemotherapy, leaving patients immunocompromised and anemic (25). Bone mineral density and collagen are decreased by prolonged disuse such as bed rest or immobilization (45,86). Recent studies have also demonstrated an increase in neutrophils, natural killer cells, and lymphocytes and a decrease in monocytes in patients subjected to 60 days of bed rest (38). Finally, bone marrow adipocytes increase in ...

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Section: Discussionmentioning

confidence: 81%

Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels

Cooper

Sell

Fahrenkrog

et al. 2016

Physiological Genomics

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“…Non-hibernating ground squirrels have 24% the plasma level of vWF as humans, and this drops an additional 10-fold during torpor (Cooper, Sell et al 2016). Human platelets have been shown to bind increased vWF in the cold (Rumjantseva, Grewal et al 2009).…”

Section: Resultsmentioning

confidence: 99%

“…Changes in vWF binding during hibernation could be due to effects of temperature, changes in ground squirrel platelets, or be due to a 10-fold decrease in vWF relative to normothermic ground squirrels (Cooper, Sell et al 2016). To isolate these three variables, a triple-cross over experiment was designed in which platelets from non-hibernating and IBA ground squirrels were incubated with shaking in plasma from both non-hibernating and IBA animals at 4°C or 37°C for 48 hours.…”

Section: Methodsmentioning

confidence: 99%

“…The hibernators will have some protection because their lower body temperatures decrease both primary and secondary hemostasis by reducing the activity of the enzymes and receptors involved in both processes (Van Poucke, Stevens et al 2014). However, hibernators have also adapted to this extreme decrease in blood flow by reversibly decreasing platelet, monocyte, neutrophil, vWF, FVIII, and FIX levels (Suomalainen and Lehto 1952, Svihla, Bowman et al 1952, Svihla, Bowman et al 1952, Svihla, Bowman et al 1953, Smith, Lewis et al 1954, Lechler and Penick 1963, Pivorun and Sinnamon 1981, Cooper, Richters et al 2012, de Vrij, Vogelaar et al 2014, Cooper, Sell et al 2016). …”

Section: Introductionmentioning

confidence: 99%

“…New platelet synthesis by megakaryocytes in the bone marrow of hibernating ground squirrels lags 24–48 hours behind arousal, indicating that platelet synthesis is also decreased during hibernation (Cooper, Richters et al 2012). However, most proteins known to be involved in platelet function did not show differential expression in the bone marrow of hibernating squirrels including the surface glycoprotein receptors ( GPIBA, GPIBB, GPIIB, GPIIIB ) and proteins found in secretory granules ( vWF, P selectin) (Cooper, Sell et al 2016). …”

Section: Introductionmentioning

confidence: 99%

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Temperature effects on the activity, shape, and storage of platelets from 13-lined ground squirrels

et al. 2017

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The objective of this study is to determine how a hibernating mammal avoids the formation of blood clots under periods of low blood flow. A microfluidic vascular injury model was performed to differentiate the effects of temperature and shear rate on platelet adhesion to collagen. Human and ground squirrel whole blood was incubated at 15 or 37°C and then passed through a microfluidic chamber over a 250 μm strip of type I fibrillar collagen at that temperature and shear rates of 50 s−1 or 300 s−1 to simulate torpid and aroused conditions respectively. At 15°C, both human and ground squirrel platelets showed a 90–95% decrease in accumulation on collagen independent of shear rate. At 37°C, human platelet accumulation reduced by 50% at 50 s−1 compared to 300 s−1, while ground squirrel platelet accumulation dropped by 80%. When compared to platelets from non-hibernating animals, platelets from animals collected after arousal from torpor showed a 60% decrease in binding at 37°C and 300 s−1, but a 2.5-fold increase in binding at 15°C and 50 s−1. vWF binding in platelets from hibernating ground squirrels were decreased by 50% relative to non-hibernating platelets. The source of the plasma that platelets were stored in did not affect the results indicating that the decreased vWF binding was a property of the platelets. Upon chilling, ground squirrel platelets increase microtubule assembly leading to the formation of long rods. This shape change is concurrent with sequestration of platelets in the liver and not the spleen. In conclusion, it appears that ground squirrel platelets are sequestered in the liver during torpor, have reduced binding capacity for plasma vWF, and lower accumulation on collagen at low shear rates and after storage at cold temperatures, while still being activated by external agonists. These adaptations would protect the animals from spontaneous thrombus formation during torpor but allow them to restore normal platelet function upon arousal.

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Comparative transcriptomics of the garden dormouse hypothalamus during hibernation

Haugg,

Borner,

Stalder

et al. 2023

FEBS Open Bio

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Torpor or heterothermy is an energy saving mechanism used by endotherms to overcome harsh environmental conditions. During winter, the garden dormouse (Eliomys quercinus) hibernates with multiday torpor bouts and body temperatures of a few degrees Celsius, interrupted by brief euthermic phases. This study investigates gene expression within the hypothalamus, the key brain area controlling energy balance, adding information on differential gene expression potentially relevant to orchestrate torpor. A de novo assembled transcriptome of the hypothalamus was generated from garden dormice hibernating under constant darkness without food and water at 5 °C. Samples were collected during early torpor, late torpor, and interbout arousal. During early torpor, 765 genes were differentially expressed as compared with interbout arousal. Twenty‐seven pathways were over‐represented, including pathways related to hemostasis, extracellular matrix organization and signaling of small molecules. Only 82 genes were found to be differentially expressed between early and late torpor, and no pathways were over‐represented. During late torpor, 924 genes were differentially expressed relative to interbout arousal. Despite the high number of differentially expressed genes, only 10 pathways were over‐represented. Of these, eight were also observed to be over‐represented when comparing early torpor and interbout arousal. Our results are largely consistent with previous findings in other heterotherms. The addition of a transcriptome of a novel species may help to identify species‐specific and overarching torpor mechanisms through future species comparisons.

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Von Willebrand factor is reversibly decreased during torpor in 13-lined ground squirrels

Cited by 16 publications

References 54 publications

Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels

Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels

Temperature effects on the activity, shape, and storage of platelets from 13-lined ground squirrels

Comparative transcriptomics of the garden dormouse hypothalamus during hibernation

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