Vascular Endothelial Growth Factor Inhibits Endothelial Cell Apoptosis Induced by Tumor Necrosis Factor-α: Balance Between Growth and Death Signals

A series of experiments was performed to determine whether vascular endothelial growth factor (VEGF), in addition to its endothelial cell specific mitogenic activity, can also protect endothelial cells from toxin-induced programmed cell death. Apoptosis was induced in endothelial cell culture with tumor necrosis factor-α(TNF-α). Simultaneous exposure of endothelial cells to VEGF resulted in a dose dependent inhibition of apoptosis when evaluated by: (1) direct counting of cells with morphologic features of apoptosis after acridine orange staining; (2) analysis of DNA fragmentation by (a) agarose gel electrophoresis and (b) fluorescence activated cell sorting (FACS); and (3) viability assays dependent upon mitochondrial function. Induction of fibronectin andβ3 integrin expression in endothelial cells by VEGF suggests that altered adhesion molecule expression may explain this survival effect.