Nuclear factor kappaB dependency of platelet-activating factor-induced angiogenesis.
Cancer Res
; 62(6): 1809-14, 2002 Mar 15.
Article
en En
| MEDLINE
| ID: mdl-11912159
ABSTRACT
This study investigated the mechanisms of platelet-activating factor (PAF)-induced angiogenesis in a mouse model of Matrigel implantation. PAF induced a dose- and time-dependent angiogenic response. Inhibitors of nuclear factor (NF) kappaB expression or action, including antisense oligonucleotides to the p65 subunit of NFkappaB (p65 antisense) and antioxidants such as alpha-tocopherol and N-acetyl-L-cysteine, significantly reduced PAF-induced angiogenesis. In human umbilical vein endothelial cells, PAF-induced mRNA expression and protein synthesis of various NFkappaB-dependent angiogenic factors, such as tumor necrosis factor-alpha, interleukin-1alpha, basic fibroblast growth factor, and vascular endothelial growth factor (VEGF). The PAF-induced expression of the above mentioned factors was inhibited by p65 antisense or antioxidants. A significant inhibition of the angiogenic effect of PAF was achieved by anti-VEGF antibodies or soluble VEGF receptors such as KDR and flt-1 but not by antibodies against tumor necrosis factor-alpha, interleukin-1alpha, or basic fibroblast growth factor. These data indicate that PAF enhances angiogenesis through inducing NFkappaB activation, which in turn promotes the production of angiogenic factors such as VEGF.
Search on Google
Banco de datos:
MEDLINE
Asunto principal:
Factor de Activación Plaquetaria
/
FN-kappa B
/
Neovascularización Fisiológica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Año:
2002
Tipo del documento:
Article