Modeled gravitational unloading induced downregulation of endothelin-1 in human endothelial cells |
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Authors: | Infanger Manfred Ulbrich Claudia Baatout Sarah Wehland Markus Kreutz Reinhold Bauer Johann Grosse Jirka Vadrucci Sonia Cogoli Augusto Derradji Hanane Neefs Mieke Küsters Sabine Spain Mike Paul Martin Grimm Daniela |
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Institution: | Department of Trauma and Reconstructive Surgery, Charité-University Medical School, Benjamin Franklin Medical Center, Center of Space Medicine, 12200 Berlin, Germany. |
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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 (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. |
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Keywords: | apoptosis cytokines endothelial cells extracellular matrix proteins cytoskeleton |
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