Modeled gravitational unloading induced downregulation of endothelin-1 in human endothelial cells.
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.
Infanger
Manfred
M
Department of Trauma and Reconstructive Surgery, Charité-University Medical School, Benjamin Franklin Medical Center, Center of Space Medicine, 12200 Berlin, Germany.
Ulbrich
Claudia
C
Baatout
Sarah
S
Wehland
Markus
M
Kreutz
Reinhold
R
Bauer
Johann
J
Grosse
Jirka
J
Vadrucci
Sonia
S
Cogoli
Augusto
A
Derradji
Hanane
H
Neefs
Mieke
M
Küsters
Sabine
S
Spain
Mike
M
Paul
Martin
M
Grimm
Daniela
D
D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D046228:Microarray Analysis; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014893:Weightlessness; D018474:Weightlessness Simulation; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D019332:Endothelin-1; D053773:Transforming Growth Factor beta1; D019014:fas Receptor; D053495:Osteopontin; D053148:Caspase 3