Anita Dittrich1,2, Daniela Grimm1,3,4, Jayashree Sahana1, Johann Bauer5, Marcus Krüger3,4, Manfred Infanger4, Nils E Magnusson2. 1. Institute of Biomedicine, Pharmacology, Aarhus University, Aarhus, Denmark. 2. Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 3. Gravitational Biology and Translational Regenerative Medicine, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany. 4. Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany. 5. Max-Planck-Institute of Biochemistry, Martinsried, Germany.
Abstract
BACKGROUND/AIMS: Cardiovascular complications are common in astronauts returning from a prolonged spaceflight. These health problems might be driven by complex modulations of gene expression and protein synthesis in endothelial cells (ECs). Studies on the influence of microgravity on phenotype, growth pattern and biological processes of ECs can help to understand these complications. METHODS: We exposed ECs (EA.hy926) to a Random Positioning Machine (RPM). Proteins associated with cell structure, angiogenesis and endothelial dysfunction were investigated in distinct pools of multicellular spheroids (MCS), adherent cells (AD) and tubular structures (TS) formed after a 35-day RPM-exposure. RESULTS: Combining morphological and molecular approaches, we found AD, MCS and TS with changes in the synthesis and release of proteins involved in three-dimensional growth. Fibronectin and monocyte chemoattractant protein-1 (MCP-1) mRNAs and protein contents were elevated along with an increased secretion of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, MCP-1, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL) and regulated on activation, normal T cell expressed and secreted (RANTES) proteins in the culture supernatant as determined by multianalyte profiling technology. Together they form a network of interaction. CONCLUSIONS: These results show that a prolonged RPM-exposure of ECs induced TS and MCS formation. The factors VEGF, NGAL, IL-6, IL-8, MCP-1, VCAM-1, ICAM-1, fibronectin and RANTES seem to be affected when gravity is omitted.
BACKGROUND/AIMS: Cardiovascular complications are common in astronauts returning from a prolonged spaceflight. These health problems might be driven by complex modulations of gene expression and protein synthesis in endothelial cells (ECs). Studies on the influence of microgravity on phenotype, growth pattern and biological processes of ECs can help to understand these complications. METHODS: We exposed ECs (EA.hy926) to a Random Positioning Machine (RPM). Proteins associated with cell structure, angiogenesis and endothelial dysfunction were investigated in distinct pools of multicellular spheroids (MCS), adherent cells (AD) and tubular structures (TS) formed after a 35-day RPM-exposure. RESULTS: Combining morphological and molecular approaches, we found AD, MCS and TS with changes in the synthesis and release of proteins involved in three-dimensional growth. Fibronectin and monocyte chemoattractant protein-1 (MCP-1) mRNAs and protein contents were elevated along with an increased secretion of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, MCP-1, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL) and regulated on activation, normal T cell expressed and secreted (RANTES) proteins in the culture supernatant as determined by multianalyte profiling technology. Together they form a network of interaction. CONCLUSIONS: These results show that a prolonged RPM-exposure of ECs induced TS and MCS formation. The factors VEGF, NGAL, IL-6, IL-8, MCP-1, VCAM-1, ICAM-1, fibronectin and RANTES seem to be affected when gravity is omitted.
Authors: Zheng-Yang Chen; Song Guo; Bin-Bin Li; Nan Jiang; Ao Li; Hong-Feng Yan; He-Ming Yang; Jin-Lian Zhou; Cheng-Lin Li; Yan Cui Journal: Biomed Res Int Date: 2019-04-03 Impact factor: 3.411
Authors: Jayashree Sahana; Thomas J Corydon; Markus Wehland; Marcus Krüger; Sascha Kopp; Daniela Melnik; Stefan Kahlert; Borna Relja; Manfred Infanger; Daniela Grimm Journal: Front Cell Dev Biol Date: 2021-06-30
Authors: Thomas J Bauer; Erich Gombocz; Markus Wehland; Johann Bauer; Manfred Infanger; Daniela Grimm Journal: Int J Mol Sci Date: 2020-03-04 Impact factor: 5.923