3D matrix‐embedding inhibits cycloheximide‐mediated sensitization to TNF‐alpha‐induced apoptosis of human endothelial cells
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nihms968212.pdf
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Accepted version
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1.3 MB
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Author(s)
Saemisch, Michael
Nickmann, Markus
Riesinger, Lisa
Edelman, Elazer R
Methe, Heiko
Date Issued
November 2017
Journal
Journal of Tissue Engineering and Regenerative Medicine
Publisher
Wiley
Citation
Saemisch, Michael, et al., "3D matrix‐embedding inhibits cycloheximide‐mediated sensitization to TNF‐alpha‐induced apoptosis of human endothelial cells." Journal of tissue engineering and regenerative medicine 12, 4 (November 2017) doi 10.1002/TERM.2609 ©2017 Author(s)
Version
Author's final manuscript
Abstract
The programmed form of cell death (apoptosis) is essential for normal development of multicellular organisms. Dysregulation of apoptosis has been linked with embryonal death and is involved in the pathophysiology of various diseases. Others and we previously demonstrated endothelial biology being intertwined with biochemical and structural composition of the subendothelial basement membrane. We now demonstrate that a three-dimensional growing environment significantly shields endothelial cells from cytokine-induced apoptosis. Detailed analysis reveals differences in intracellular signaling pathways in naive endothelial cells and cytokine-stimulated endothelial cells when cells are grown within a three-dimensional collagen-based matrix compared to cells grown on two-dimensional tissue culture plates. Main findings are significantly reduced p53 expression and level of p38-phosphorylation in three-dimensional grown endothelial cells. Despite similar concentrations of focal adhesion kinase, three-dimensional matrix-embedded endothelial cells express significantly less tyrosine-phosphorylated focal adhesion kinase. Pretreatment with antibodies against integrin αvβ3 partially reversed the protective effect of three-dimensional matrix-embedding on endothelial apoptosis. Our findings provide detailed insights into the mechanisms of endothelial apoptosis with respect to the spatial matrix environment. These results enhance our understanding of endothelial biology and may otherwise help in the design of tissue-engineered materials. Furthermore, findings on focal adhesion kinase phosphorylation might enhance our understanding of clinical studies with tyrosine kinase inhibitors. ©2017
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
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DOI of Published Version
https://doi.org/10.1002/TERM.2609
