Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor-alpha: 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-alpha (TNF-alpha). 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 and beta 3 integrin expression in endothelial cells by VEGF suggests that altered adhesion molecule expression may explain this survival effect.
Spyridopoulos
I
I
St Elizabeth's Medical Center, Department of Medicine, Boston, MA 02134, USA.
Brogi
E
E
Kearney
M
M
Sullivan
A B
AB
Cetrulo
C
C
Isner
J M
JM
Losordo
D W
DW
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D008934:Mitogens / Q000494:pharmacology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors