| Autor: |
Jokšienė J; Laboratory of Preclinical Drug Investigation, Institute of Cardiology, Lithuanian University of Health Sciences, Sukileliu Ave. 15, LT-50162 Kaunas, Lithuania.; Department of Biomedicine, The Faculty of Health, Aarhus University, Ole Worms Allé 4, 8000 Aarhus, Denmark., Sahana J; Department of Biomedicine, The Faculty of Health, Aarhus University, Ole Worms Allé 4, 8000 Aarhus, Denmark., Wehland M; Department of Microgravity and Translational Regenerative Medicine, Medical Faculty, Otto von Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany., Schulz H; Department of Microgravity and Translational Regenerative Medicine, Medical Faculty, Otto von Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany., Cortés-Sánchez JL; Department of Microgravity and Translational Regenerative Medicine, Medical Faculty, Otto von Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany., Prat-Duran J; Department of Biomedicine, The Faculty of Health, Aarhus University, Ole Worms Allé 4, 8000 Aarhus, Denmark., Grimm D; Department of Biomedicine, The Faculty of Health, Aarhus University, Ole Worms Allé 4, 8000 Aarhus, Denmark.; Department of Microgravity and Translational Regenerative Medicine, Medical Faculty, Otto von Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany.; Research Group 'Magdeburger Arbeitsgemeinschaft für Forschung unter Raumfahrt- und Schwerelosigkeitsbedingungen' (MARS), Otto von Guericke University, 39106 Magdeburg, Germany., Simonsen U; Department of Biomedicine, The Faculty of Health, Aarhus University, Ole Worms Allé 4, 8000 Aarhus, Denmark. |
| Abstrakt: |
A diabetogenic state induced by spaceflight provokes stress and health problems in astronauts. Microgravity (µ g ) is one of the main stressors in space causing hyperglycaemia. However, the underlying molecular pathways and synergistic effects of µ g and hyperglycaemia are not fully understood. In this study, we investigated the effects of high glucose on EA.hy926 endothelial cells in simulated µ g (s-µ g ) using a 3D clinostat and static normogravity (1 g ) conditions. After 14 days of cell culture under s-µ g and 1 g conditions, we compared the expression of extracellular matrix (ECM), inflammation, glucose metabolism, and apoptosis-related genes and proteins through qPCR, immunofluorescence, and Western blot analyses, respectively. Apoptosis was evaluated via TUNEL staining. Gene interactions were examined via STRING analysis. Our results show that glucose concentrations had a weaker effect than altered gravity. µ g downregulated the ECM gene and protein expression and had a stronger influence on glucose metabolism than hyperglycaemia. Moreover, hyperglycaemia caused more pronounced changes in 3D cultures than in 2D cultures, including bigger and a greater number of spheroids, upregulation of NOX4 and the apoptotic proteins NF-κB and CASP3, and downregulation of fibronectin and transglutaminase-2. Our findings bring new insights into the possible molecular pathways involved in the diabetogenic vascular effects in µ g . |
