Modeled gravitational unloading induced downregulation of endothelin-1 in human endothelial cells.

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Authors

  • Manfred Infanger
  • Claudia Ulbrich
  • Sarah Baatout
  • Markus Wehland
  • Reinhold Kreutz
  • Johann Bauer
  • Jirka Grosse
  • Sonia Vadrucci
  • Augusto Cogoli
  • Hanane Derradji
  • Mieke Neefs
  • Sabine Kusters
  • Mike Spain
  • Martin Paul
  • Daniela Grimm

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Abstract

Many space missions have shown that prolonged space flights may increase the risk of cardiovascular problems. Using a three-dimensional clinostat, we investigated human endothelial EA.hy926 cells up to 10 days under conditions of simulated microgravity to distinguish transient from long-term effects of 0g. Maximum expression of all selected genes occurred after 10 minutes of clinorotation. Gene expression (osteopontin, Fas, TGF-ß) declined to slightly upregulated levels or rose again (caspase-3) after the fourth day of clinorotation. Caspase-3, Bax and Bcl-2 protein content was enhanced for 10 days of microgravity. In addition, long-term accumulation of collagen type I and III and alterations of the cytoskeletal alpha- and beta-tubulins and F-actin were detectable. A significantly reduced release of soluble factors in simulated microgravity was measured for brain-derived neurotrophic factor, tissue factor, VEGF and interestingly for endothelin-1, which is important in keeping cardiovascular balances. The gene expression of endothelin-1 was suppressed under 0g conditions at day 7 and 10. Alterations of the vascular endothelium together with a decreased release of endothelin-1 may entail post-flight health hazards for astronauts.

Details

Original languageEnglish
Pages (from-to)1439-1455
JournalJournal of Cellular Biochemistry
Volume101
Issue number6
DOIs
Publication statusPublished - 23 Aug 2007

Keywords

  • microgravity, space, endothelial cells

ID: 126703