3D matrix ‐embedding inhibits cycloheximide‐mediated sensitization to TNF‐alpha‐induced apoptosis of human endothelial cells

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 endo...
Source: Journal of Tissue Engineering and Regenerative Medicine - Category: Biotechnology Authors: Tags: RESEARCH ARTICLE Source Type: research