Skip to main content

Advertisement

SpringerLink
Log in

Molecular and Cellular Characterization of Space Flight Effects on Microvascular Endothelial Cell Function – PreparatoryWork for the SFEF Project

  • Original Article
  • Published:
Microgravity Science and Technology Aims and scope Submit manuscript

Abstract

Exposure to microgravity during space flight (SF) of variable length induces suffering of the endothelium (the cells lining all blood vessels), mostly responsible for health problems found in astronauts and animals returning from space. Of interest to pre-nosological medicine, the effects of microgravity on astronauts are strikingly similar to the consequences of sedentary life, senescence and degenerative diseases on Earth, although SF effects are accelerated and reversible. Thus, microgravity is a significant novel model for better understanding of common pathologies. A comprehensive cell and molecular biology study is needed in order to explain pathophysiological findings after SFs. This project will study the effects of microgravity and cosmic radiation on endothelial cells (ECs) cultured on the International Space Station through analysis of 1) cell transcriptome, 2) DNA methylome, 3) DNA damage and cell senescence, 4) variations in cell cycle and cell morphology. This project has been selected by the European Space Agency and the Italian Space Agency and is presently in preparation. The ground study presented here was performed to determine the biological and engineering requirements that will allow us to retrieve suitable samples after culturing, fixing and storing ECs in space. We expect to identify molecular pathways activated by space microgravity in microvascular ECs, which may shed light on pathogenic molecular mechanisms responsible for endothelial suffering shared by astronauts and individuals affected with aging, degenerative and sedentary life-associated pathologies on Earth.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ades, E.W., Candal, F.J., Swerlick, R.A., George, V.G., Summers, S., Bosse, D.C., Lawley, T.J.: HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J. Invest. Dermatol. 99(6), 683–90 (1992)

    Article  Google Scholar 

  • Andreassi, M.G.: DNA damage, vascular senescence and atherosclerosis. J. Mol. Med. 86, 1033–43 (2008)

    Article  Google Scholar 

  • Augustin, H.G., Kozian, D.H., Johnson, R.C.: Differentiation of endothelial cells: analysis of 582 the constitutive and activated endothelial cell phenotypes. Bioessays 16(12), 901–6 (1994)

    Article  Google Scholar 

  • Buravkova, L.B., Romanov, Y.A.: The role of cytoskeleton in cell changes under condition of simulated microgravity. Acta Astronaut. 48, 647–650 (2001)

    Article  Google Scholar 

  • Buravkova, L., Romanov, Y., Rykova, M., Grigorieva, O., Merzlikina, N.: Cell-to cell interactions in changed gravity: ground-based and flight experiments. Acta Astronaut. 57, 67–74 (2005)

    Article  Google Scholar 

  • Carlsson, S.I., Bertilaccio, M.T., Ascari, I., Bradamante, S., Maier, J.A.: Modulation of human endothelial cell behaviour in simulated microgravity. J. Gravit. Physiol. 9, 273–4 (2002)

    Google Scholar 

  • Carlsson, S.I., Bertilaccio, M.T., Ballabio, E., Maier, E.A.: Endothelial stress by gravitational unloading: effects on cell growth and cytoskeletal organization. Biochim. Biophys. Acta. 1642, 173–9 (2003)

    Article  Google Scholar 

  • Cines, D.B., Pollak, E.S., Buck, C.A., Loscalzo, J., Zimmerman, G.A., McEver, R.P., Pober, J.S., Wick, T.M., Konkle, B.A., Schwartz, B.S., Barnathan, E.S., McCrae, K.R., Hug, B.A., Schmidt, A.M., Stern, D.M.: Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91(10), 3527–61 (1998)

    Google Scholar 

  • Cotrupi, S., Maier, J.A.: Is HSP70 upregulation crucial for cellular proliferative response in simulated microgravity?. J. Gravit. Physiol. 11, P173–176 (2004)

    Google Scholar 

  • Cotrupi, S., Ranzani, D., Maier, J.A.: Impact of modeled microgravity on microvascular endothelial cells. Biochim. Biophys. Acta. 1746, 163–8 (2005)

    Article  Google Scholar 

  • Coupé, M., Fortrat, J.O., Larina, I., Gauquelin-Koch, G., Gharib, C., Custaud, M.A.: Cardiovascular deconditioning: From autonomic nervous system to microvascular dysfunctions. Respir. Physiol. Neurobiol., 169 (2009). Suppl 1:S10–S12

  • Danese, S., Dejana, E., Fiocchi, C.: Immune regulation by microvascular endothelial cells: directing innate and adaptive immunity, coagulation, and inflammation. J. Immunol. 178(10), 6017–22 (2007)

    Article  Google Scholar 

  • Davidson, J.M., Aquino, A.M., Woodward, S.C., Wilfinger, W.W.: Sustained microgravity reduces intrinsic wound healing and growth factor responses in the rat. FASEB J. 13(2), 325–329 (1999)

    Google Scholar 

  • Demiot, C., Dignat-George, F., Fortrat, J.O., Sabatier, F., Gharib, C., Larina, I., Gauquelin-Koch, G., Hughson, R., Custaud, M.A.: WISE 2005: chronic bed rest impairs microcirculatory endothelium in women. Am. J. Physiol. Heart Circ. Physiol. 293(5), H3159–64 (2007)

    Article  Google Scholar 

  • Fishman, A.P.: Endothelium: a distributed organ of diverse capabilities. Ann. N Y Acad. Sci. 401, 1–8 (1982)

    Article  Google Scholar 

  • Grenon, S.M., Jeanne, M., Aguado-Zuniga, J., Conte, M.S., Hughes-Fulford, M.: Effects of gravitational mechanical unloading in endothelial cells: association between caveolins, inflammation and adhesion molecules. Sci. Rep. 3, 1494 (2013)

    Article  Google Scholar 

  • Griffoni, C., Di Molfetta, S., Fantozzi, L., Zanetti, C., Pippia, P., Tomasi, V., Spisni, E.: Modification of proteins secreted by endothelial cells during modeled low gravity exposure. J. Cell Biochem. 112(1), 265–72 (2011)

    Article  Google Scholar 

  • Grimm, D., Bauer, J., Kossmehl, P., Shakibaei, M., Schöberger, J., Pickenhahn, H., Schulze-Tanzil, G., Vetter, R., Eilles, C., Paul, M., Cogoli, A.: Simulated microgravity alters differentiation and increases apoptosis in human follicular thyroid carcinoma cells. FASEB J. 16(6), 604–6 (2002)

    Google Scholar 

  • Grimm, D., Infanger, M., Westphal, K., Ulbrich, C., Pietsch, J., Kossmehl, P., Vadrucci, S., Baatout, S., Flick, B., Paul, M., Bauer, J.: A delayed type of three-dimensional growth of human endothelial cells under simulated weightlessness. Tissue Eng. Part A. 15(8), 2267–75 (2009)

    Article  Google Scholar 

  • Grosse J., Wehland, M., Pietsch, J., Ma, X., Ulbrich, C., Schulz, H., Saar, K., Hubner, N., Hauslage, J., Hemmersbach, R., Braun, M., Van Loon, J., Vagt, N., Infanger, M., Eilles, C., Egli, M., Richter, P., Baltz, T., Einspanier, R., Sharbati, S., Grimm, D.: Short-term weightlessness produced by parabolic flight maneuvers altered gene expression patterns in human endothelial cells. FASEB J. 26, 639–655 (2012)

    Article  Google Scholar 

  • Hammond, T.G., Lewis, F.C., Goodwin, T.J., Linnehan, R.M., Wolf, D.A., Hire, K.P., Campbell, W.C., Benes, E., O’Reilly, K.C., Globus, R.K., Kaysen, J.H.: Gene expression in space. Nat. Med. 5(4), 359 (1999)

    Article  Google Scholar 

  • Henry, M.K., Unsworth, B.R., Sychev, V., Guryeva, T.S., Dadasheva, O.A., Piert, S.J., Lagel, K.E., Dubrovin, L.C., Jahns, G.C., Boda, K., Sabo, V., Samet, M.M., Lelkes, P.I.: Launch conditions might affect the formation of blood vessels in the quail chorioallantoic membrane. Folia Vet. 42 (1998). Suppl:S25–31

  • Herranz, R., Anken, R., Boonstra, J., Braun, M., Christianen, P.C., De Geest, M., Hauslage, J., Hilbig, R., Hill, R.J., Lebert, M., Medina, F.J., Vagt, N., Ullrich, O., Van Loon, J.J., Hemmersbach R.: Ground-based facilities for simulation of microgravity: organism-specific recommendations for their use, and recommended terminology. Astrobiology. 13(1), 1–17 (2013)

    Article  Google Scholar 

  • Igarashi, K., Miura, M.: Inhibition of a radiation-induced senescence-like phenotype: a possible mechanism for potentially lethal damage repair in vascular endothelial cells. Radiat. Res. 170, 534–9 (2008)

    Article  Google Scholar 

  • Infanger, M., Kossmehl, P., Shakibaei, M., Baatout, S., Witzing, A., Grosse, J., Bauer, J., Cogoli, A., Faramarzi, S., Derradji, H., Neefs, M., Paul, M., Grimm, D.: Induction of three-dimensional assembly and increase in apoptosis of human endothelial cells by simulated microgravity: impact of vascular endothelial growth factor. Apoptosis 11(5), 749–64 (2006)

    Article  Google Scholar 

  • Kapitonova, M.Y., Muid, S., Froemming, G.R., Yusoff, W.N., Othman, S., Ali, A.M., Nawawi, H.M.: Real space flight travel is associated with ultrastructural changes, cytoskeletal disruption and premature senescence of HUVEC. Malays. J. Pathol. 34(2), 103–13 (2012)

    Google Scholar 

  • Kirchen, M.E., O’Connor, K.M., Gruber, H.E., Sweeney, J.R., Fras, I.A., Stover, S.J., Sarmiento, A., Marshall, G.J.: Effects of microgravity on bone healing in a rat fibular osteotomy model. Clin. Orthop. Relat. Res. 318, 231–42 (1995)

    Google Scholar 

  • Kusumbe, A.P., Ramasamy, S.K., Adams R.H.: Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature 507(7492), 323–8 (2014)

    Article  Google Scholar 

  • Ma, X., Pietsch, J., Wehland, M., Schulz, H., Saar, K., Hübner, N., Bauer, J., Braun, M., Schwarzwälder, A., Segerer, J., Birlem, M., Horn, A., Hemmersbach, R., Waßer, K., Grosse, J., Infanger, M., Grimm, D.: Differential gene expression profile and altered cytokine secretion of thyroid cancer cells in space. FASEB J. 28(2), 813–35 (2014)

    Article  Google Scholar 

  • Manti, L.: Does reduced gravity alter cellular response to ionizing radiation?. Radiat. Environ. Biophys. 45(1), 1–8 (2006)

    Article  Google Scholar 

  • Mariotti, M., Maier, J.A.: Gravitational unloading induces an anti-angiogenic phenotype in human microvascular endothelial cells. J. Cell Biochem. 104, 129–35 (2008)

    Article  Google Scholar 

  • Mariotti, M., Maier, J.A.M.: Human Micro-and Macrovascular endothelial cells exposed to simulated microgravity upregulate hsp70. Microgravity Sci. Tech. 21, 141–144 (2009)

    Article  Google Scholar 

  • Monahan-Earley, R., Dvorak, A.M., Aird, W.C.: Evolutionary origins of the blood vascular system and endothelium. J. Thromb. Haemost. 11(1), 46–66 (2013)

    Article  Google Scholar 

  • Morbidelli, L., Monici, M., Marziliano, N., Cogoli, A., Fusi, F., Waltenberger, J., Ziche, M.: Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals. Biochem. Biophys. Res. Commun. 334(2), 491–9 (2005)

    Article  Google Scholar 

  • Nolan, D.J., Ginsberg, M., Israely, E., Palikuqi, B., Poulos, M.G., James, D., Ding, B.S., Schachterle, W., Liu, Y., Rosenwaks, Z., Butler, J.M., Xiang, J., Rafii, A., Shido, K., Rabbany, S.Y., Elemento, O., Rafii, S.: Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration. Dev. Cell 26(2), 204–19 (2013)

    Article  Google Scholar 

  • Norsk, P.: Cardiovascular research in space. Respir. Physiol. Neurobiol. 169(1), S2–3 (2009)

    Article  Google Scholar 

  • Pietsch, J., Ma, X., Wehland, M., Aleshcheva, G., Schwarzwälder, A., Segerer, J., Birlem, M., Horn, A., Bauer, J., Infanger, M., Grimm D.: Spheroid formation of human thyroid cancer cells in an automated culturing system during the Shenzhou-8 Space mission. Biomaterials 34(31), 7694–705 (2013)

    Article  Google Scholar 

  • Riley, D.A., Ilyina-Kakueva, E.I., Ellis, S., Bain, J.L., Slocum, G.R, Sedlak, F.R.: Skeletal muscle fiber, nerve, and blood vessel breakdown in space-flown rats. FASEB J. 4(1), 84–91 (1990)

    Google Scholar 

  • Romanov, Y., Kabaeva, N., Buravkova, L.: Simulated hypogravity stimulates cell spreading and wound healing in cultured human vascular endothelial cells. J. Gravit. Physiol. 7, 77–8 (2000)

    Google Scholar 

  • Sanford, G.L., Ellerson, D., Melhado-Gardner, C., Sroufe, A.E., Harris-Hooker, S.: Three-dimensional growth of endothelial cells in the microgravity-based rotating wall vessel bioreactor. In Vitro Cell. Dev. Biol. Anim. 38, 493–504 (2002)

    Article  Google Scholar 

  • Shi, F., Wang, Y.C., Zhao, T.Z., Zhang, S., Du, T.Y., Yang, C.B., Li, Y.H., Sun, X.Q.: Effects of simulated microgravity on human umbilical vein endothelial cell angiogenesis and role of the PI3K-Akt-eNOS signal pathway. PLoS One. 7(7), e40365 (2012)

    Article  Google Scholar 

  • Siamwala, J.H., Majumder, S., Tamilarasan, K.P., Muley, A., Reddy, S.H., Kolluru, G.K., Sinha, S., Chatterjee, S.: Simulated microgravity promotes nitric oxide-supported angiogenesis via the iNOS-cGMP-PKG pathway in macrovascular endothelial cells. FEBS Lett. 584(15), 3415–23 (2010)

    Article  Google Scholar 

  • Siamwala, J.H., Reddy, S.H., Majumder, S., Kolluru, G.K., Muley, A., Sinha, S., Chatterjee, S.: Simulated microgravity perturbs actin polymerization to promote nitric oxide-associated migration in human immortalized Eahy926 cells. Protoplasma 242(1-4), 3–12 (2010)

    Article  Google Scholar 

  • Singh, K.P., Kumari, R., Dumond, J.W.: Simulated microgravity-induced epigenetic changes in human lymphocytes. J. Cell Biochem. 111(1), 123–9 (2010)

    Article  Google Scholar 

  • Vernikos, J., Schneider, V.S.: Space, gravity and the physiology of aging: parallel or convergent disciplines?. Gerontology 56(2), 157–66 (2010)

    Article  Google Scholar 

  • Versari, S., Longinotti, G., Barenghi, L., Maier, J.A., Bradamante, S.: The challenging environment on board the International Space Station affects endothelial cell function by triggering oxidative stress through thioredoxin interacting protein overexpression: the ESA-SPHINX experiment. FASEB J. 27(11), 4466–75 (2013)

    Article  Google Scholar 

  • Versari, S., Villa, A., Bradamante, S., Maier, J.A.: Alterations of the actin cytoskeleton and increased nitric oxide synthesis are common features in human primary endothelial cell response to changes in gravity. Biochim. Biophys. Acta. 1773, 1645–52 (2007)

    Article  Google Scholar 

  • Villa, A., Versari, S., Maier, J.A., Bradamante S: Cell behavior in simulated microgravity: a comparison of results obtained with RWV and RPM. Gravit. Space Biol. Bull. 18(2), 89–90 (2005)

    Google Scholar 

  • Warnke, E., Pietsch, J., Wehland, M., Bauer, J., Infanger, M., Görög, M., Hemmersbach, R., Braun, M., Ma, X., Sahana, J., Grimm, D.: Spheroid formation of human thyroid cancer cells under simulated microgravity: a possible role of CTGF and CAV1. Cell Commun. Signal., 12:32 (2014)

Download references

Acknowledgments

The authors are grateful to J.A.M. Maier and S. Versari for helpful discussion and hints, and to Ms. Alison Frank for text editing. This work was supported by the European Space Agency, the Agenzia Spaziale Italiana (contract number 5681), Regione Toscana (POR FSE 2007-2013-FORTEC), Kayser Italia S.r.l., to DA.

Author information

Author notes

  1. Alessandra Merenda

    Present address: Cambridge Stem Cell Institute, Cambridge, UK

Authors and Affiliations

  1. Institute of Life Sciences, Scuola Superiore Sant’Anna, Pisa, Italy

    Michele Balsamo, Ivana Barravecchia, Sara Mariotti & Debora Angeloni

  2. University of Pisa, Pisa, Italy

    Alessandra Merenda & Chiara De Cesari

  3. Kayser Italia S.r.l., Livorno, Italy

    Marco Vukich

  4. IFC CNR Research Area, Via G. Moruzzi, 1-56124, Pisa, Italy

    Debora Angeloni

Authors
  1. Michele Balsamo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ivana Barravecchia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sara Mariotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alessandra Merenda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chiara De Cesari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marco Vukich
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Debora Angeloni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Debora Angeloni.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Balsamo, M., Barravecchia, I., Mariotti, S. et al. Molecular and Cellular Characterization of Space Flight Effects on Microvascular Endothelial Cell Function – PreparatoryWork for the SFEF Project. Microgravity Sci. Technol. 26, 351–363 (2014). https://doi.org/10.1007/s12217-014-9399-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12217-014-9399-4

Keywords

Search

Navigation