Nuclear factor kappaB 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 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.
Ko
Hyun-Mi
HM
Department of Biological Sciences, The Institute of Basic Sciences, Research Institute of Medical Science, Chonnam National University, Kwangju 500-757, Japan.
Seo
Kook Heon
KH
Han
Su-Ji
SJ
Ahn
Kyu Youn
KY
Choi
Il-Hwan
IH
Koh
Gou Young
GY
Lee
Hern-Ku
HK
Ra
Myung Suk
MS
Im
Suhn-Young
SY
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000975:Antioxidants; D016228:Endothelial Growth Factors; D006133:Growth Substances; D008222:Lymphokines; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors