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

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

    Research outputpeer-review


    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.
    Original languageEnglish
    Pages (from-to)1439-1455
    JournalJournal of Cellular Biochemistry
    Issue number6
    StatePublished - 23 Aug 2007

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