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

J Cell Biochem. 2007 Aug 15;101(6):1439-55. doi: 10.1002/jcb.21261.

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 (microg) to distinguish transient from long-term effects of microg and 1g. Maximum expression of all selected genes occurred after 10 min of clinorotation. Gene expression (osteopontin, Fas, TGF-beta(1)) 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, vascular endothelial growth factor (VEGF), and interestingly for endothelin-1, which is important in keeping cardiovascular balances. The gene expression of endothelin-1 was suppressed under microg conditions at days 7 and 10. Alterations of the vascular endothelium together with a decreased release of endothelin-1 may entail post-flight health hazards for astronauts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Cytoskeleton / metabolism
  • Cytoskeleton / ultrastructure
  • Down-Regulation
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Microarray Analysis
  • Osteopontin / genetics
  • Osteopontin / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Weightlessness
  • Weightlessness Simulation*
  • fas Receptor / genetics
  • fas Receptor / metabolism

Substances

  • Cytokines
  • Endothelin-1
  • Transforming Growth Factor beta1
  • fas Receptor
  • Osteopontin
  • Caspase 3