PDF herunterladen
Thromb Haemost 2009; 101(05): 902-910
DOI: 10.1160/TH08-11-0750
Platelets and Blood Cells
Schattauer GmbH

Effects of microgravity and hypergravity on platelet functions

Kesheng Dai
1   Department of Biological Science and Technology, Beijing University of Aeronautics and Astronautics, Beijing, China
,
Yuedan Wang
2   Department of Immunology, Peking University, Beijing, China
,
Rong Yan
1   Department of Biological Science and Technology, Beijing University of Aeronautics and Astronautics, Beijing, China
,
Quanwei Shi
1   Department of Biological Science and Technology, Beijing University of Aeronautics and Astronautics, Beijing, China
,
Zhicheng Wang
1   Department of Biological Science and Technology, Beijing University of Aeronautics and Astronautics, Beijing, China
,
Yanhong Yuan
1   Department of Biological Science and Technology, Beijing University of Aeronautics and Astronautics, Beijing, China
3   Space Cell and Molecular Biology Laboratory, China Astronaut Research and Training Center, Beijing, China
,
Hong Cheng
1   Department of Biological Science and Technology, Beijing University of Aeronautics and Astronautics, Beijing, China
,
Suping Li
1   Department of Biological Science and Technology, Beijing University of Aeronautics and Astronautics, Beijing, China
,
Yubo Fan
1   Department of Biological Science and Technology, Beijing University of Aeronautics and Astronautics, Beijing, China
,
Fengyuan Zhuang
1   Department of Biological Science and Technology, Beijing University of Aeronautics and Astronautics, Beijing, China
› InstitutsangabenFinancial support: This work was supported by grants from National Natural Science Foundation of China (NSFC 30770795), Program for New Century Excellent Talents in University (NCET-06–0167), and A Foundation for the Author of National Excellent Doctoral Dissertation of P.R. China (FANEDD 200560).
Weitere Informationen

Publikationsverlauf

Received: 17. November 2008

Accepted after major revision: 28. Januar 2009

Publikationsdatum:
24. November 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Summary

Many serious thrombotic and haemorrhagic diseases or fatalities have been documented in human being exposed to micro-gravity or hypergravity environments, such as crewmen in space, roller coaster riders, and aircrew subjected to high-G training. Some possible related organs have been examined to explore the mechanisms underlying these gravity change-related diseases. However, the role of platelets which are the primary players in both thrombosis and haemostasis is unknown. Here we show that platelet aggregation induced by ristocetin or collagen and platelet adhesion to von Willebrand factor (VWF) were significantly decreased after platelets were exposed to simulated microgravity. Conversely, these platelet functions were increased after platelets were exposed to hypergravity. The tail bleeding time in vivo was significantly shortened in mice exposed to high-G force, whereas, was prolonged in hindlimb unloaded mice. Furthermore, three of 23 mice died after 15 minutes of –8 Gx stress. Platelet thrombi disseminated in the heart ventricle and blood vessels in the brain, lung, and heart from the dead mice. Finally, glycoprotein (GP) Ibα surface expression and its association with the cytoskeleton were significantly decreased in platelets exposed to simulated microgravity, and obviously increased in hypergravity-exposed platelets. These data indicate that the platelet functions are inhibited in microgravity environments, and activated under high-G conditions, suggesting a novel mechanism for gravity change-related haemorrhagic and thrombotic diseases. This mechanism has important implications for preventing and treating gravity change-related diseases, and also suggests that special attentions should be paid to human actions under different gravity conditions.

Keywords

Platelets - thrombosis - haemorrhage - simulated microgravity - hypergravity
 

  • References

  • 1 Rowe WJ. The Apollo 15 Space Syndrome. Circulation 1998; 97: 119-120.
    CrossrefPubMedGoogle Scholar
  • 2 Rowe WJ. Interplanetary travel and permanent injury to normal heart. Acta Astronaut 1997; 40: 719-722.
    CrossrefPubMedGoogle Scholar
  • 3 Pelletier AR, Gilchrist J. Roller coaster related fatalities, United States, 1994–2004. Inj Prev 2005; 11: 309-312.
    CrossrefPubMedGoogle Scholar
  • 4 Braksiek RJ, Roberts DJ. Amusement park injuries and deaths. Ann Emerg Med 2002; 39: 65-72.
    CrossrefPubMedGoogle Scholar
  • 5 Cayce WR, Zerull RG. Myocardial infarction occurring at the conclusion of centrifuge training in a 37-year-old aviator. Aviat Space Environ Med 1992; 63: 1106-1108.
    PubMedGoogle Scholar
  • 6 Perrier E, Manen O, Cinquetti G. Essential thrombocytosis and myocardial infarction in an aircrew member: aeromedical concerns. Aviat Space Environ Med 2006; 77: 69-72.
    PubMedGoogle Scholar
  • 7 Riley DA, Ellis S, Giometti CS. et al. Muscle sarcomere lesions and thrombosis after spaceflight and suspension unloading. J Appl Physiol 1992; 73: 33S-43S.
    CrossrefPubMedGoogle Scholar
  • 8 Fuse A, Aoki Y, Sato T. et al. Decreased platelet level in peripheral blood of mice by microgravity. Biol Sci Space 2002; 16: 159-160.
    PubMedGoogle Scholar
  • 9 Watenpaugh DE. Fluid volume control during short-term space flight and implications for human performance. J Exp Biol 2001; 204: 3209-3215.
    PubMedGoogle Scholar
  • 10 Pringle SD, Macfarlane PW, Cobbe SM. Response of heart rate to a roller coaster ride. Br Med J 1989; 299: 1575.
    CrossrefPubMedGoogle Scholar
  • 11 Nencini P, Basile AM, Sarti C. et al. Cerebral hemorrhage following a roller coaster ride. J Am Med Assoc 2000; 284: 832-833.
    CrossrefPubMedGoogle Scholar
  • 12 Smith DH, Meaney DF. Roller coasters, g forces, and brain trauma: on the wrong track?. J Neurotrauma 2002; 19: 1117-2220.
    CrossrefPubMedGoogle Scholar
  • 13 Huizinga EG, Tsuji S, Romijn RA. et al. Structures of Glycoprotein Ibα and Its Complex with von Wille-brand Factor A1 Domain. Science 2002; 297: 1176-1179.
    CrossrefPubMedGoogle Scholar
  • 14 Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or trans-location on von Willebrand factor. Cell 1996; 84: 289-297.
    CrossrefPubMedGoogle Scholar
  • 15 Kasirer-Friede A, Cozzi MR, Mazzucato M. et al. Signalling through GP Ib-IX-V activates alpha IIb beta 3 independently of other receptors. Blood 2004; 103: 3403-3411.
    CrossrefPubMedGoogle Scholar
  • 16 Mazzucato M, Pradella P, Cozzi MR. et al. Sequential cytoplasmic calcium signals in a 2-stage platelet activation process induced by the glycoprotein Ibalpha mechanoreceptor. Blood 2002; 100: 2793-2800.
    CrossrefPubMedGoogle Scholar
  • 17 Merten M, Thiagarajan P. P-selectin in arterial thrombosis. Z Kardiol 2004; 93: 855-863.
    CrossrefPubMedGoogle Scholar
  • 18 Moake JL. Thrombotic thrombocytopenic purpura: the systemic clumping “plague.”. Annu Rev Med 2002; 53: 75-88.
    CrossrefPubMedGoogle Scholar
  • 19 Ruan CG, Du XP, Xi XD. et al. A murine antiglyco-protein Ib complex monoclonal antibody, SZ 2, inhibits platelet aggregation induced by both ristocetin and collagen. Blood 1987; 69: 570-577.
    PubMedGoogle Scholar
  • 20 Wu G, Xi X, Li P. et al. Preparation of a monoclonal antibody, SZ-51, that recognizes an alpha-granule membrane protein (GMP-140) on the surface of activated human platelets. Nouv Rev Fr Hematol 1990; 32: 231-235.
    PubMedGoogle Scholar
  • 21 Clement JQ, Lacy SM, Wilson BL. Genome-wide gene expression profiling of microgravity effect on human liver cells. J Gravit Physiol 2007; 14: 121-122.
    PubMedGoogle Scholar
  • 22 Hammond TG, Hammond JM. Optimized suspension culture: the rotating-wall vessel. Am J Physiol Renal Physiol 2001; 281: F12-25.
    CrossrefPubMedGoogle Scholar
  • 23 Saxena R, Pan G, McDonald JM. Osteoblast and osteoclast differentiation in modeled microgravity. Ann N Y Acad Sci 2007; 1116: 494-498.
    CrossrefPubMedGoogle Scholar
  • 24 Morey-Holton ER, Globus RK. The hindlimb unloading rodent model: technical aspects. J Appl Physiol 2002; 92: 1367-1377.
    PubMedGoogle Scholar
  • 25 Jung CK, Chung S, Lee YY. et al. Monocyte adhesion to endothelial cells increases with hind-limb unloading in rats. Aviat Space Environ Med 2005; 76: 720-725.
    PubMedGoogle Scholar
  • 26 Lee EH, Ding W, Kulkarni AD. et al. Tumor growth and immune function in mice during hind-limb unloading. Aviat Space Environ Med 2005; 76: 536-540.
    PubMedGoogle Scholar
  • 27 Mueller PJ, Foley CM, Heesch CM. et al. Increased nitric oxide synthase activity and expression in the hypothalamus of hindlimb unloaded rats. Brain Res 2006; 1115: 65-74.
    CrossrefPubMedGoogle Scholar
  • 28 Dai K, Bodnar R, Berndt MC. et al. A critical role for 14–3–3zeta protein in regulating the VWF binding function of platelet glycoprotein Ib-IX and its therapeutic implications. Blood 2005; 106: 1975-1981.
    CrossrefPubMedGoogle Scholar
  • 29 Li Z, Xi X, Gu M. et al. A stimulatory role for cGMP-dependent protein kinase in platelet activation. Cell 2003; 112: 77-86.
    CrossrefPubMedGoogle Scholar
  • 30 Fox JE. Cytoskeletal proteins and platelet signaling. Thromb Haemost 2001; 86: 198-213.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 31 Fox JE. The platelet cytoskeleton. Thromb Haemost 1993; 70: 884-893.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 32 Storey RF, Newby LJ, Heptinstall S. Effects of P2Y(1) and P2Y(12) receptor antagonists on platelet aggregation induced by different agonists in human whole blood. Platelet 2001; 12: 443-447.
    PubMedGoogle Scholar
  • 33 Bakaltcheva I, Gyimah D, Reid T. Effects of alpha-tocopherol on platelets and the coagulation system. Platelets 2001; 12: 389-394.
    CrossrefPubMedGoogle Scholar
  • 34 Williamson D, Pikovski I, Cranmer SL. et al. Interaction between platelet glycoprotein Ibalpha and filamin-1 is essential for glycoprotein Ib/IX receptor anchorage at high shear. J Biol Chem 2002; 277: 2151-2159.
    CrossrefPubMedGoogle Scholar
  • 35 Feng S, Reséndiz JC, Lu X. et al. Filamin A binding to the cytoplasmic tail of glycoprotein Ibalpha regulates von Willebrand factor-induced platelet activation. Blood 2003; 102: 2122-2129.
    CrossrefPubMedGoogle Scholar
  • 36 Cunningham JG, Meyer SC, Fox JEB. The Cytoplasmic Domain of the a-subunit of glycoprotein (GP) Ib mediates attachment of the entire GP Ib-IX Complex to the cytoskeleton and regulates von Willebrand factor-induced changes in cell morphology. J Biol Chem 1996; 271: 11581-11587.
    CrossrefPubMedGoogle Scholar
  • 37 Fredrickson BJ, Dong JF, McIntire LV. et al. Shear-dependent rolling on von Willebrand factor of mammalian cells expressing the platelet glycoprotein Ib-IX-V complex. Blood 1998; 92: 3684-3693.
    PubMedGoogle Scholar
  • 38 Kuschyk J, Haghi D, Borggrefe M. et al. Cardiovascular response to a modern roller coaster ride. J Am Med Assoc 2007; 298: 739-741.
    PubMedGoogle Scholar
  • 39 Dintenfass L. Experiment on “Discovery” STS 51-C: aggregation of red cells and thrombocytes in heart disease, hyperlipidaemia and other conditions. Adv Space Res 1989; 09: 65-69.
    PubMedGoogle Scholar
  • 40 Surgenor DM, Kevy SV, Chao FC. et al. Human blood cells at microgravity: the NASA Initial Blood Storage Experiment. Transfusion 1990; 30: 605-616.
    CrossrefPubMedGoogle Scholar
  • 41 Schmitt DA, Ohlmann P, Gachet C. et al. Platelet shape change and protein phosphorylation induced by ADP and thrombin are not sensitive to short periods of microgravity. J Cell Sci 1993; 104: 805-810.
    PubMedGoogle Scholar
  • 42 Riley DA, Ilyina-Kakueva EI, Ellis S. et al. Skeletal muscle fiber, nerve, and blood vessel breakdown in space-flown rats. FASEB J 1990; 04: 84-91.
    CrossrefPubMedGoogle Scholar