Skip to main content
Log in

The Effect of Long-term Space Flights on Human Urine Proteins Functionally Related to Endothelium

  • Published:
Human Physiology Aims and scope Submit manuscript

Abstract

It is known that long-term space flights lead to dysregulation of the cardiovascular system, and the endothelium is the most important functional element of such dysregulation. In order to find the signs of endothelial dysfunction in cosmonauts who have been in long-term space flights, we collected urine samples from 21 cosmonauts before the flight and on the first and seventh days after landing. The urine samples were investigated by chromatography–mass spectrometry analysis. Proteins were identified using the MaxQuant software and the SwissProt database. The software package Perseus was used for semi-quantitative analysis. The reconstruction of associative molecular networks was performed using the ANDSystem software. We identified 200 different proteins in urine samples of 21 Russian cosmonauts. The ANDSystem software made it possible to determine seven processes related to endothelium functioning. These processes had direct relations to 17 urine proteins, which were functionally associated with the endothelium. At the same time, eight proteins (such as serotransferrin, prostate-specific antigen, fibrinogen gamma chain, UFO tyrosine kinase receptor, aminopeptidase N, vascular cell adhesion molecule 1, osteopontin, and syndecan-4) were significantly changed (p < 0.01) at different points of the recovery period (the first and seventh days). Thus, we performed the first study of the urine protein composition in cosmonauts for the evaluation of signs of endothelial dysfunction after space flight using proteomics methods.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bogomolov, V.V. and Samarin, G.I., Improvement of the medical support system for the health and work efficiency of the crews of the International Space Station, Kosmonavtika Raketostr., 2007, no. 4 (49), p. 48.

    Google Scholar 

  2. Kotovskaya, A.R. and Fomina, G.A., Characteristics of adaptation and maladaptation of human cardiovascular system under space flight conditions, Hum. Physiol., 2010, vol. 36, no. 2, p. 190.

    Article  Google Scholar 

  3. Rudimov, E.G., Secretory and adhesive properties of human endothelial cells in modeling effects of microgravity in vitro, Extended Abstract of Cand. Sci. (Biol.) Dissertation, Moscow, 2015, p. 27.

    Google Scholar 

  4. Sofronova, S.I., Tarasova, O.S., Gaynullina, D., et al., Spaceflight on the Bion-M1 biosatellite alters cerebral artery vasomotor and mechanical properties in mice, J. Appl. Physiol., 2015, vol. 118, no. 7, p. 830.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Delp, M.D., Charvat, J.M., Limoli, C.L., et al., Apollo lunar astronauts show higher cardiovascular disease mortality: possible deep space radiation effects on the vascular endothelium, Sci. Rep., 2016, vol. 28, no. 6, p. 29901. doi 10.1038/srep29901

    Article  Google Scholar 

  6. Kashirina, D., Pastushkova, L., Custaud, M.A., et al., Effect of 21-day head down bed rest on urine proteins related to endothelium: correlations with changes in carbohydrate metabolism, Acta Astronaut., 2017, vol. 137, p. 122.

    Article  CAS  Google Scholar 

  7. Pretnar-Oblak, J., Cerebral endothelial function determined by cerebrovascular reactivity to L-arginine, Biomed. Res. Int., 2014, vol. 2014, p. 601515. doi 10.1155/2014/601515

    Article  PubMed  PubMed Central  Google Scholar 

  8. Romanov, Yu.A., Kabaeva, N.V., and Buravkova, L.B., Gravitation sensitivity of human endothelium, Aviakosm. Ekol. Med., 2000, vol. 34, no. 4, p. 23.

    Google Scholar 

  9. Michiels, C., Endothelial cell functions, J. Cell Physiol., 2003, vol. 196, no. 3, p. 430.

    Article  CAS  PubMed  Google Scholar 

  10. Gamboa, A., Abraham, R., Diedrich, A., et al., Role of adenosine and nitric oxide on the mechanisms of action of dipyridamole, Stroke, 2005, vol. 36, no. 10, p. 2170.

    Article  CAS  PubMed  Google Scholar 

  11. Verigo, Ya.I., Demko, I.V., Petrova, M.M., et al., The von Willebrand factor and its role in endothelial dysfunction in ischemic heart disease, Sib. Med. Obozr., 2014, no. 5 (89), p. 23.

    Google Scholar 

  12. Boerma, M., Nelson, G.A., Sridharan, V., et al., Space radiation and cardiovascular disease risk, World J. Cardiol., 2015, vol. 7, no. 12, p. 882. doi 10.4330/ wjc.v7.i12.882

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mischak, H., Thongboonkerd, V., Schanstra, J.P., and Vlahou, A., Renal and urinary proteomics, Proteomics Clin. Appl., 2011, vol. 5, nos. 5–6, p. 211. doi 10.1002/prca.201190031

    CAS  PubMed  Google Scholar 

  14. Metzger, J., Negm, A.A., Plentz, R.R., et al., Urine proteomic analysis differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders, Gut, 2013, vol. 62, no. 1, p. 122. doi 10.1136/gutjnl-2012-302047

    Article  CAS  PubMed  Google Scholar 

  15. Valeeva, O.A., Pastushkova, L.Kh., Pakharukova, N.A., Dobrokhotov, I.V., and Larina, I.M., Variability of urine proteome in healthy humans during a 105-day isolation in a pressurized compartment, Hum. Physiol., 2011, vol. 37, no. 3, p. 351.

    Article  CAS  Google Scholar 

  16. Ivanisenko, V.A., Saik, O.V., Ivanisenko, N.V., et al., ANDSystem: an associative network discovery system for automated literature mining in the field of biology, BMC Syst. Biol., 2015, vol. 9, no. 2, p. S2. doi 10.1186/1752-0509.9

    Article  PubMed  PubMed Central  Google Scholar 

  17. Berendeeva, T.A., The analysis of the level of cytokines in a healthy person during space flight factors and their ground modeling, Extended Abstract of Cand. Sci. (Med.) Dissertation, Moscow, 2010, p. 22.

    Google Scholar 

  18. Morukov, B.V., Rykova, M.P., Antropova, E.N., Berendeeva, T.A., Ponomaryov, S.A., and Larina, I.M., Parameters of the innate and adaptive immunity in cosmonauts after long-term space flight on board the international space station, Hum. Physiol., 2010, vol. 36, no. 3, p. 264.

    Article  CAS  Google Scholar 

  19. Gustafsson, A., Martuszewska, D., Johansson, M., et al., Differential expression of Axl and Gas6 in renal cell carcinoma reflecting tumor advancement and survival, Clin Cancer Res., 2009, vol. 15, no. 14, p. 4742. doi 10.1158/1078-0432.CCR-08-2514

    Article  CAS  PubMed  Google Scholar 

  20. Cook-Mills, J.M., Johnson, J.D., Deem, T.L., et al., Calcium mobilization and Rac1 activation are required for VCAM-1 (vascular cell adhesion molecule-1) stimulation of NADPH oxidase activity, Biochem J., 2004, vol. 378, no. 2, p. 539.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gershovich, P.M., Gershovich, Yu.G., and Buravkova, L.B., Cytoskeleton structure and adhesion properties of human stromal precursors under conditions of simulated microgravity, Cell Tissue Biol., 2009, vol. 3, p. 423.

    Article  Google Scholar 

  22. Romanov, Y.A., Buravkova, L.B., Rikova, M.P., et al., Expression of cell adhesion molecules and lymphocyte- endothelium interaction under simulated hypogravity in vitro, J. Gravitational Physiol., 2001, vol. 8, no. 1, p. 5.

    Google Scholar 

  23. Buravkova, L., Romanov, Y., Rykova, M., et al., Cellto- cell interactions in changed gravity: Ground-based and flight experiments, Acta Astronaut., 2005, vol. 57, p. 67.

    Article  CAS  PubMed  Google Scholar 

  24. Muid, S., Froemming, G.R.A., Manaf, A., et al., Changes in protein and gene expression of adhesion molecules and cytokines of endothelial cells immediately following short-term spaceflight travel, Gravitational Space Biol., 2010, vol. 23, no. 2, p. 1.

    Google Scholar 

  25. Liu, H., Wang, Z.C., Yue, Y., et al., Simulated microgravity induces an inflammatory response in the common carotid artery of rats, Can J. Physiol. Pharmacol., 2014, vol. 92, no. 8, p. 661.

    Article  CAS  PubMed  Google Scholar 

  26. Gasanov, A.G. and Bershova, T.V., The role of changes of the extracellular matrix in the occurrence of cardiovascular diseases, Biomed. Khim., 2009, vol. 55, no. 2, p. 155.

    CAS  PubMed  Google Scholar 

  27. Du, P., Suhaeri, M., Subbiah, R., et al., Elasticity modulation of fibroblast-derived matrix for endothelial cell vascular morphogenesis and mesenchymal stem cell differentiation, Tissue Eng., Part A, 2016, vol. 22, nos. 5–6, p. 415. doi 10.1089/ten.TEA.2015.0503

    Article  CAS  Google Scholar 

  28. Tamura, A., Shingai, M., Aso, N., et al., Osteopontin is released from the heart into the coronary circulation in patients with a previous anterior wall myocardial infarction, Circ. J., 2003, vol. 67, no. 9, p. 742.

    Article  CAS  PubMed  Google Scholar 

  29. Satoh, M., Nakamura, M., Akatsu, T., et al., Myocardial osteopontin expression is associated with collagen fibrillogenesis in human dilated cardiomyopathy, Eur. J. Heart Failure, 2005, vol. 7, no. 5, p. 755.

    Article  CAS  Google Scholar 

  30. Teng, Y.H.-F., Aquino, R.S., and Park, P.W., Molecular functions of syndecan-1 in disease, Matrix Biol., 2012, vol. 31, p. 3.

    Article  CAS  PubMed  Google Scholar 

  31. Jakobsson, L., Kreuger, J., Holmborn, K., et al., Heparan sulfate in trans potentiates VEGFR-mediated angiogenesis, Dev. Cell, 2006, vol. 10, p. 625.

    Article  CAS  PubMed  Google Scholar 

  32. Multhaupt, H.A., Yoneda, A., Whiteford, J.R., et al., Syndecan signaling: when, where and why? J. Physiol. Pharmacol., 2009, vol. 60, suppl 4, p. 31.

    PubMed  Google Scholar 

  33. Vuong, T.T., Reine, T.M., Sudworth, A., et al., Syndecan- 4 is a major syndecan in primary human endothelial cells in vitro, modulated by inflammatory stimuli and involved in wound healing, J. Histochem. Cytochem., 2015, vol. 63, no. 4, p. 280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kumar, S., Sharma, P., Bansal, A., et al., Hypobaric hypoxia-mediated protein expression in plasma of susceptible & tolerant rats, Indian J. Med. Res., 2014, vol. 140, p. 756.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Orlov, Yu.P., Lukach, V.N., Dolgikh, V.T., et al., Pathogenetic significance of the failured iron metabolism in the development of microcirculatory disorders during reperfusion: experimental study, Sib. Med. Zh., 2012, no. 5, p. 71.

    Google Scholar 

  36. Ivanova, S.M., The blood system during space flight conditions and after, in Orbital’naya stantsiya Mir. Kosmicheskaya biologiya i meditsina. Tom 2. Mediko-biologicheskie eksperimenty (Orbital Station Mir. Space Biology and Medicine, Vol. 2: Medical-Biological Experiments), Moscow: Anikom, 2002, p. 159.

    Google Scholar 

  37. Kapitonova, M.Yu., Kuznetsov, S.L., Froemming, G.R.A., Muid, S., Nor-Ashikin, M.N.K., Otman, S., Shahir, A.R.M., and Nawawi, H., Effects of space mission factors on the morphology and function of endothelial cells, Bull. Exp. Biol. Med., 2013, vol. 154, no. 6, p. 796.

    Article  PubMed  Google Scholar 

  38. Carlsson, S.I., Bertilaccio, M.T., Ballabio, E., et al., Endothelial stress by gravitational unloading: effects on cell growth and cytoskeletal organization, Biochim. Biophys. Acta, 2003, vol. 1642, no. 3, p. 173.

    Article  CAS  PubMed  Google Scholar 

  39. Lewis, M.L., Reynolds, J.L., Cubano, L.A., et al., Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat), FASEB J., 1998, vol. 12, no. 11, p. 1007.

    Article  CAS  PubMed  Google Scholar 

  40. Yarovaya, G.A. and Neshkova, A.E., Past and present research on the kallikrein-kinin system (on the 90th anniversary of the discovery of the system), Russ. J. Bioorg. Chem., 2015, vol. 41, no. 3, p. 245.

    Article  CAS  Google Scholar 

  41. Pul’bere, S.A., Diseases of the prostate, differential diagnosis, and prognosis of the outcome, Doctoral (Med.) Dissertation, Moscow, 2015.

    Google Scholar 

  42. Dorofeev, S.D., Kudryavtsev, Yu.V., and Kudryavtseva, L.V., Immunohistochemical aspects of chronic abacterial prostatitis, Eff. Farmakoter., Urol. Nefrol., 2014, no. 2, p. 26.

    Google Scholar 

  43. Alexandrova, S.A. and Pinaev, G.P., Actin cytoskeleton reorganization in bone marrow multipotent mesenchymal stromal cells at the initial step of transendothelial migration, Biophysics, 2014, vol. 59, no. 5, p. 741.

    Article  CAS  Google Scholar 

  44. Subramani, J., Ghosh, M., Rahman, M.M., et al., Tyrosine phosphorylation of CD13 regulates inflammatory cell–cell adhesion and monocyte trafficking, J. Immunol., 2013, vol. 191, no. 7, p. 3905.

    Article  CAS  PubMed  Google Scholar 

  45. Ghosh, M., Jaganathan, S., Rahman, M.M., and Shapiro, L.H., CD13 restricts TLR4 endocytic signal transduction in inflammation, J. Immunol., 2015, vol. 194, no. 9, p. 4466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mitrofanov, K.Yu., Zhelankin, A.V., and Sazonova, M.A., Association of nuclear genome mutations with the development of myocardial infarction, Ateroskler. Dislipidemii, 2013, no. 2 (11), p. 56.

    Google Scholar 

  47. Paton, L.N., Mocatta, T.J., Richards, A.M., and Winterbourn, C.C., Increased thrombin-induced polymerization of fibrinogen associated with high protein carbonyl levels in plasma from patients post myocardial infarction, Free Radic. Biol. Med., 2010, vol. 48, no. 2, p. 223. doi 10.1016/j.freeradbiomed.2009.10.044

    Article  CAS  PubMed  Google Scholar 

  48. Korotkova, N.V., Activity of cathepsins l and n in diseases of the veins of the lower extremities, Cand. Sci. (Med.) Dissertation, Moscow, 2015.

    Google Scholar 

  49. Korchagina, A.A., Shein, S.A., Gurina, O.I., and Chekhonin, V.P., VEGFRS in neoplastic angiogenesis and prospects for therapy of brain tumors, Vestn. Ross. Akad. Med. Nauk, 2013, vol. 68, no. 11, p. 104.

    Article  Google Scholar 

  50. Arthur, J.S. and Ley, S.C., Mitogen-activated protein kinases in innate immunity, Nat. Rev. Immunol., 2013, vol. 3, no. 9, p. 679.

    Article  Google Scholar 

  51. Kuzichkin, D.S., Morukov, B.V., Markin, A.A., Juravlyova, O.A., Zabolotskaya, I.V., and Vostrikova, L.V., Hemostasis system indices after short-term space flights and during 7-day “dry” immersion experiment, Hum. Physiol., 2010, vol. 36, no. 4, p. 478.

    Article  Google Scholar 

  52. Gonzales, P.A., Pisitkun, T., Hoffert, J.D., et al., Large-scale proteomics and phosphoproteomics of urinary exosomes, J. Am. Soc. Nephrol., 2009, vol. 20, no. 2, p. 363. doi 10.1681/ASN.2008040406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. Kh. Pastushkova.

Additional information

Original Russian Text © L.Kh. Pastushkova, D.N. Kashirina, A.S. Kononikhin, A.G. Brzhozovsky, V.A. Ivanisenko, E.S. Tiys, A.M. Novosyolova, M.-A. Custaud, E.N. Nikolaev, I.M. Larina, 2018, published in Fiziologiya Cheloveka, 2018, Vol. 44, No. 1, pp. 72–81.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pastushkova, L.K., Kashirina, D.N., Kononikhin, A.S. et al. The Effect of Long-term Space Flights on Human Urine Proteins Functionally Related to Endothelium. Hum Physiol 44, 60–67 (2018). https://doi.org/10.1134/S0362119718010139

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0362119718010139

Keywords

Navigation