Angiogenesis endothelial cells

Inhibitors of IkBo phosphorylation have been described which irreversibly inhibit cytokine-induced phosphorylation without affecting constitutive phosphorylation. One such compound (Bay 11-7083 ((E)3-[4-f-butylphenyl)-sulfonyl]-2-propenenitrile)) was found to be effective in two animal models of inflammation after intraperitoneal administration [89]. In addition to the effect it has on the expression of adhesion molecules in pro-inflammatory responses, inhibition of the transcription factor NFkB will also have an effect on angiogenesis. Endothelial cells can produce growth factors and cytokines which have pro-angiogenic effects. Some of these factors, e.g. IL-8, TNFa and MCP-1 are known to be produced via NFkB-mediated endothelial cell activation [90,91]. The importance of NFKB-mediated responses in pro-angiogenic endothelium was reflected in studies in which the NFkB inhibitor PDTC decreased retinal neovascularization in the eye of mice [92]. 

Reliable markers are needed to monitor the activity of antiangiogenic dtugs. Circulating endothelial cells and their progenitor subset are a potential candidate, as is MRI dynamic measurement of vascular permeability/ flow in response to angiogenesis inhibitors, but neither has been clinically validated. 

Salcedo R, Oppenheim JJ. Role of chemokines in angiogenesis CXCL12/SDF-1 and CXCR4 interaction, a key regulator of endothelial cell responses. Microcirculation 2003 10(3-4) 359-370. 

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