title: Apoptosis inducers endotoxin and Fas-ligation enhance the expression of vascular endothelial growth factor in human endothelial cells.
abstract: Endothelial cells in culture were exposed during four hours to the apoptosis inducing agents endotoxin (lipopolysaccharide, LPS) and Fas-ligand mimicking antibody in various concentrations. With addition of a deletion primer as internal standard a competitive RT-PCR was performed to measure semi-quantitatively the expression of mRNA of Vascular endothelial growth factor (VEGF). It appeared that endothelial cells survive increasing amounts of LPS and show a concentration- and time-dependent increase in the expression of VEGF-mRNA. The same effect was found with Fas-ligation, although at high concentrations Fas-ligation induced no further increase, but even a decrease of VEGF expression, possibly related to cell damage. Apoptotic cells were rarely observed after LPS-stimulation, but simultaneous incubation with a blocking antibody to VEGF resulted in a significant increase in apoptosis. We hypothesize that endothelial cells are resistant to apoptosis induction by autocrine expression of VEGF under stress conditions.
authors.affiliation: Department of Clinical Chemistry, Medisch Spectrum Twente, Enschede, The Netherlands.
authors.forename: P T
authors.initials: PT
authors.lastname: Marx
authors.forename: A B
authors.initials: AB
authors.lastname: Mulder
authors.forename: F A
authors.initials: FA
authors.lastname: Van Den Bergh
authors.forename: R
authors.initials: R
authors.lastname: Overbeeke
authors.forename: C
authors.initials: C
authors.lastname: Haanen
authors.forename: I
authors.initials: I
authors.lastname: Vermes
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019014:fas Receptor / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D016228:Endothelial Growth Factors; D008070:Lipopolysaccharides; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019014:fas Receptor