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Microgravity Science and Technology

, Volume 21, Issue 1–2, pp 135–140 | Cite as

Effect of Hypergravity on Endothelial Cell Function and Gene Expression

  • Lucia MorbidelliEmail author
  • Nicola Marziliano
  • Venere Basile
  • Silvia Pezzatini
  • Giovanni Romano
  • Antonio Conti
  • Monica Monici
Original Article

Abstract

It is well known that endothelial cells (ECs), which play a major role in cardiovascular system functioning, are very sensitive to mechanical stimuli. It has been demonstrated that changes in inertial conditions (i.e. microgravity and hypergravity) can affect both phenotypic and genotypic expression in ECs. In this report we describe the effects of hypergravity on ECs isolated from bovine aorta (BAECs). ECs were repeatedly exposed to discontinuous hypergravity conditions (5 × 10 min at 10×g with 10 min at 1×g between sets), simulated in a hyperfuge. Then, cell morphology and metabolism were analyzed by autofluorescence techniques. The phenotypic expression of cytoskeleton constituents (β-actin, vimentin, tubulin), adhesion and survival signals (integrins), mediators of inflammation and angiogenesis was evaluated by immunocytofluorescence. Quantitative PCR (Q-PCR) with Low Density Arrays (LDAs) was used to evaluate modifications in gene expression. After hypergravity exposure, no significant changes were observed in cell morphology and energy metabolism. Cells remained adherent to the substratum, but integrin distribution was modified. Accordingly, the cytoskeletal network reorganized, documenting cell activation. There was a reduction in expression of genes controlling vasoconstriction and inflammation. Proapoptotic signals were downregulated. On the whole, the results documented that hypergravity exposure maintained EC survival and function by activation of adaptive mechanisms.

Keywords

Hypergravity Endothelial cells Mechanotransduction 

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References

  1. Ali, M.H., Schumacker, P.T.: Endothelial responses to mechanical stress: where is the mechanosensor? Crit. Care Med. 30, S198 (2002)CrossRefGoogle Scholar
  2. Carlsson, S.J., Bertilaccio, M.T., Ballabio, E., Maier, J.A.: Endothelial stress by gravitational unloading: effects on cell growth and cytoskeletal organization. Biochimica et Biophysica Acta. 1642, 173 (2003)Google Scholar
  3. Cho, R.J., Campbell, M.J.: Transcription, genomes, function. Trends Genet. 16, 409 (2000)CrossRefGoogle Scholar
  4. Livak, K.J., Schmittgenb, T.D.: Analysis of relative gene expression data using real time quantitative PCR and the 2 − ΔΔCt method. Methods. 25, 402 (2001)CrossRefGoogle Scholar
  5. Monici, M.: Cell and tissues autofluorescence. Research and diagnostic applications. Biotechnol. Annu. Rev. 11, 227 (2005)CrossRefGoogle Scholar
  6. Monici, M., Marziliano, N., Basile, V., Pezzatini, S., Romano, G., Conti, A., Morbidelli, L.: Hypergravity affects morphology and function in microvascular endothelial cells. Microgravity Sci. Technol. 18, 234 (2006)CrossRefGoogle Scholar
  7. 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, 491 (2005)CrossRefGoogle Scholar
  8. Pezzatini, S., Morbidelli, L., Solito, R., Paccagnini, E., Boanini, E., Bigi, A., Ziche, M.: Nanostructured HA crystals up-regulate FGF-2 expression and activity in microvascular endothelium promoting angiogenesis. Bone. 41(4), 523 (2007)CrossRefGoogle Scholar
  9. Spisni, E., Bianco, M.C., Griffoni, C., Toni, M., d’Angelo, R., Santi, S., Riccio, M., Tomasi, V.: Mechanosensing role of caveolae and caveolar constituents in human endothelial cells. J. Cell. Physiol. 197, 198 (2003)CrossRefGoogle Scholar
  10. Sumanasekera, W.K., Sumanasekera, G.U., Mattingly, K.A., Dougherty, S.M., Keynton, R.S., Klinge, C.M.: Estradiol and dihydrotestosterone regulate endothelial cell barrier function after hypergravity-induced alterations in MAPK activity. Am. J. Physiol. Cell Physiol. 293(2), C566 (2007)CrossRefGoogle Scholar
  11. Sumanasekera, W.K., Zhao, L., Ivanova, M., Morgan, D.D., Noisin, E.L., Keynton, R.S., Klinge, C.M.: Effect of estradiol and dihydrotestosterone on hypergravity-induced MAPK signaling and occludin expression in human umbilical vein endothelial cells. Cell Tissue Res. 324(2), 243 (2006)CrossRefGoogle Scholar
  12. 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. Biochimica et Biophysica Acta. 1773(11), 1645 (2007)Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Lucia Morbidelli
    • 1
    Email author
  • Nicola Marziliano
    • 2
  • Venere Basile
    • 3
  • Silvia Pezzatini
    • 1
  • Giovanni Romano
    • 3
  • Antonio Conti
    • 3
  • Monica Monici
    • 4
  1. 1.Section of Pharmacology, Department of Molecular BiologyUniversity of SienaSienaItaly
  2. 2.IRCCSFoundation San Matteo HospitalPaviaItaly
  3. 3.Department of Clinical PhysiopathologyUniversity of FlorenceFlorenceItaly
  4. 4.ASACampus, Div. Ricerca di ASA, c/o Dept. of Clinical PhysiopathologyUniversity of FlorenceFlorenceItaly

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