PMID- 29402845 OWN - NLM STAT- MEDLINE DCOM- 20180326 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 45 IP - 2 DP - 2018 TI - Key Proteins Involved in Spheroid Formation and Angiogenesis in Endothelial Cells After Long-Term Exposure to Simulated Microgravity. PG - 429-445 LID - 10.1159/000486920 [doi] AB - 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. CI - (c) 2018 The Author(s). Published by S. Karger AG, Basel. FAU - Dittrich, Anita AU - Dittrich A AD - Institute of Biomedicine, Pharmacology, Aarhus University, Aarhus, Denmark. AD - Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Grimm, Daniela AU - Grimm D AD - Institute of Biomedicine, Pharmacology, Aarhus University, Aarhus, Denmark. AD - Gravitational Biology and Translational Regenerative Medicine, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany. AD - Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany. FAU - Sahana, Jayashree AU - Sahana J AD - Institute of Biomedicine, Pharmacology, Aarhus University, Aarhus, Denmark. FAU - Bauer, Johann AU - Bauer J AD - Max-Planck-Institute of Biochemistry, Martinsried, Germany. FAU - Kruger, Marcus AU - Kruger M AD - Gravitational Biology and Translational Regenerative Medicine, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany. AD - Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany. FAU - Infanger, Manfred AU - Infanger M AD - Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany. FAU - Magnusson, Nils E AU - Magnusson NE AD - Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. LA - eng PT - Journal Article DEP - 20180124 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL5) RN - 0 (Fibronectins) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) RN - 0 (Lipocalin-2) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 0 (Vascular Endothelial Growth Factor A) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - A549 Cells MH - Cell Adhesion MH - Cell Culture Techniques/instrumentation MH - Cell Fusion MH - Cell Line MH - Chemokine CCL2/genetics/metabolism MH - Chemokine CCL5/analysis MH - Fibronectins/genetics/metabolism MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Intercellular Adhesion Molecule-1/metabolism MH - Interleukin-6/analysis MH - Interleukin-8/analysis MH - Lipocalin-2/analysis MH - *Neovascularization, Physiologic MH - Spheroids, Cellular/cytology/*metabolism MH - Up-Regulation MH - Vascular Cell Adhesion Molecule-1/metabolism MH - Vascular Endothelial Growth Factor A/metabolism MH - *Weightlessness Simulation OTO - NOTNLM OT - Angiogenesis OT - Endothelial cells OT - Endothelial dysfunction OT - Microgravity OT - Multicellular spheroids OT - Random Positioning Machine OT - Tube formation EDAT- 2018/02/07 06:00 MHDA- 2018/03/27 06:00 CRDT- 2018/02/07 06:00 PHST- 2017/09/25 00:00 [received] PHST- 2017/12/10 00:00 [accepted] PHST- 2018/02/07 06:00 [pubmed] PHST- 2018/03/27 06:00 [medline] PHST- 2018/02/07 06:00 [entrez] AID - 000486920 [pii] AID - 10.1159/000486920 [doi] PST - ppublish SO - Cell Physiol Biochem. 2018;45(2):429-445. doi: 10.1159/000486920. Epub 2018 Jan 24.