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

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.

Growing Tissues in Real and Simulated Microgravity: New Methods for Tissue Engineering

“…104 Similar effects have also been reported in further studies. 105 More importantly, Ea.hy926 cells readily formed 3D multicellular spheroids similar to those observed on RWVs within the first 24 h of incubation on the RPM. 53,104 Between the 5th and the 7th day of growth on the RPM, double-row cell assemblies were forming.…”

Key Proteins Involved in Spheroid Formation and Angiogenesis in Endothelial Cells After Long-Term Exposure to Simulated Microgravity

“…A recent study showed that ras homolog gene family member A (RhoA) inactivation supports the actin rearrangement-associated angiogenic responses in human umbilical vein endothelial cells (HUVECs) during simulated microgravity [7]. Early cytoskeletal changes of microgravity-exposed ECs have previously been described in real and simulated microgravity [10, 11]. …”

The Impact of Altered Gravity and Vibration on Endothelial Cells During a Parabolic Flight

“…Furthermore, when exposed to altered gravity conditions, EC showed strong reactions ranging from alterations in cytoskeletal arrangement and gene expression after only 22 s of real microgravity to long-term effects such as formation of defined 3D structures on the Random Positioning Machine (RPM), a device which aims to simulate microgravity on Earth by randomly rotating the sample around all three axes in space, and thereby cancels out the effect of the gravity vector over time [6,7,8,9,10,11]. Some of these 3D structures assume tubular shapes resembling vascular intimas and recent studies have shown that these structures are a promising basis toward the systematic tissue engineering of vessels [12,13].…”