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Apoptosis

, Volume 11, Issue 5, pp 749–764 | Cite as

Induction of three-dimensional assembly and increase in apoptosis of human endothelial cells by simulated microgravity: Impact of vascular endothelial growth factor

  • M. Infanger
  • P. Kossmehl
  • M. Shakibaei
  • S. Baatout
  • A. Witzing
  • J. Grosse
  • J. Bauer
  • A. Cogoli
  • S. Faramarzi
  • H. Derradji
  • M. Neefs
  • M. Paul
  • D. Grimm
Article

Abstract

Endothelial cells play a crucial role in the pathogenesis of many diseases and are highly sensitive to low gravity conditions. Using a three-dimensional random positioning machine (clinostat) we investigated effects of simulated weightlessness on the human EA.hy926 cell line (4, 12, 24, 48 and 72 h) and addressed the impact of exposure to VEGF (10 ng/ml). Simulated microgravity resulted in an increase in extracellular matrix proteins (ECMP) and altered cytoskeletal components such as microtubules (alpha-tubulin) and intermediate filaments (cytokeratin). Within the initial 4 h, both simulated microgravity and VEGF, alone, enhanced the expression of ECMP (collagen type I, fibronectin, osteopontin, laminin) and flk-1 protein. Synergistic effects between microgravity and VEGF were not seen. After 12 h, microgravity further enhanced all proteins mentioned above. Moreover, clinorotated endothelial cells showed morphological and biochemical signs of apoptosis after 4 h, which were further increased after 72 h. VEGF significantly attenuated apoptosis as demonstrated by DAPI staining, TUNEL flow cytometry and electron microscopy. Caspase-3, Bax, Fas, and 85-kDa apoptosis-related cleavage fragments were clearly reduced by VEGF. After 72 h, most surviving endothelial cells had assembled to three-dimensional tubular structures. Simulated weightlessness induced apoptosis and increased the amount of ECMP. VEGF develops a cell-protective influence on endothelial cells exposed to simulated microgravity.

Keywords

apoptosis endothelial cells extracellular matrix proteins microgravityl VEGF weightlessness 

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • M. Infanger
    • 1
  • P. Kossmehl
    • 2
  • M. Shakibaei
    • 3
    • 4
  • S. Baatout
    • 5
  • A. Witzing
    • 2
  • J. Grosse
    • 2
  • J. Bauer
    • 6
  • A. Cogoli
    • 7
  • S. Faramarzi
    • 2
  • H. Derradji
    • 5
  • M. Neefs
    • 5
  • M. Paul
    • 2
  • D. Grimm
    • 2
    • 8
  1. 1.Department of Trauma and Reconstructive Surgery, Benjamin Franklin Medical Center Center of Space Medicine BerlinCharité-University Medical SchoolBerlinGermany
  2. 2.Institute of Clinical Pharmacology and Toxicology, Center of Space MedicineCharité-University Medical SchoolBerlinGermany
  3. 3.Institute of AnatomyCharité-University Medical SchoolBerlin
  4. 4.Institute of AnatomyLudwig-Maximilians-UniversityMunichGermany
  5. 5.Laboratory of RadiobiologyBelgian Nuclear Research CentreMolBelgium
  6. 6.Max-Planck Institute of BiochemistryMartinsriedGermany
  7. 7.Zero-g Lifetec GmbHTechnopark, ETH ZurichZurichSwitzerland
  8. 8.Institute of Clinical Pharmacology and ToxicologyCharit-University MedicineBerlinGermany

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