Vascular endothelial growth factor inhibits programmed cell death of endothelial cells induced by clinorotation.
The principal aim of this study was to investigate short- and long-term effects of clinorotation on human endothelial cells (EA hy 926 cell line) using a three-dimensional random positioning machine. Moreover, the impact of vascular endothelial growth factor (VEGF) was addressed. Immediately, within one hour and after four and twenty-four hours an increase of apoptotic cells was detected. VEGF significantly inhibited the amount of apoptotic endothelial cells (EC). VEGF reduced the amount of fas-positive EC. Moreover, after 24 hours, proliferating EC grew in form of three-dimensional multicellular spheroids and also as monolayers. The initially formed spheroids (maximum diameter 3 mm) remained stable up to the 15th day of clinorotation. Some spheroids revealed tubular structures. In addition, a clear increase of extracellular matrix proteins such as osteopontin and fibronectin was measured. The three-dimensional clinostat represents an important tool for cell biological experiments. VEGF significantly attenuated the changes of endothelial cells induced by simulated weightlessness in a cell protective manner.
Infanger
Manfred
M
Department of Trauma and Reconstructive Surgery, Charité Unviersity Medicine Berlin, Germany. Manfred.Infanger@charite.de
Kossmehl
Peter
P
Shakibaei
Mehdi
M
Cogoli
Augusto
A
Witzing
Adam
A
Faramarzi
Shideh
S
Wittfoht
Werner
W
Paul
Martin
M
Grimm
Daniela
D
D017209:Apoptosis / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D008856:Microscopy, Fluorescence; D012399:Rotation; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D018474:Weightlessness Simulation
D016326:Extracellular Matrix Proteins; D042461:Vascular Endothelial Growth Factor A