Nuclear Factor B Dependency of Platelet-activating Factor-induced Angiogenesis

This study investigated the mechanisms of platelet-activating factor (PAF)-induced angiogenesis in a mouse model of Matrigel implantation. PAF induced a doseand time-dependent angiogenic response. Inhibitors of nuclear factor (NF) B expression or action, including antisense oligonucleotides to the p65 subunit of NF B (p65 antisense) and antioxidants such as -tocopherol and N-acetyl-L-cysteine, significantly reduced PAFinduced angiogenesis. In human umbilical vein endothelial cells, PAFinduced mRNA expression and protein synthesis of various NF Bdependent angiogenic factors, such as tumor necrosis factor, interleukin-1 , 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, interleukin-1 , or basic fibroblast growth factor. These data indicate that PAF enhances angiogenesis through inducing NF B activation, which in turn promotes the production of angiogenic factors such as VEGF.