Antiangiogenesis efficacy of nitric oxide donors

Angiogenesis is a complex process involving endothelial cell migration, pro liferation, invasion, and tube formation. Inhibition of these processes mig ht have implications in various angiogenesis-mediated disorders. Because ni tric oxide (NO) is known to play a key role in various vascular diseases, t he present study was undertaken to determine the role of NO in angiogenesis -mediated processes using the NO donor, S-nitroso N-acetyl penicillamine (S NAP) and S-nitroso N-acetyl glutathione (SNAG). The antiangiogenic efficacy of these NO donors was examined using in vivo and in vitro model systems. The in vitro studies demonstrated the ability of SNAP to inhibit cytokine f ibroblast growth factor (FGF2)-stimulated tube formation and serum-induced cell proliferation. The inhibitory effect on cell proliferation by SNAP con centrations above the millimolar range was associated with significant shif ts in the concentration of NO metabolites. Furthermore, using the mouse Mat rigel implant model and the chick chorioallantoic membrane (CAM) models, SN AP demonstrated maximal inhibitory efficacy (85-95% inhibition) of cytokine (FGF2)induced neovascularization in both in vivo models. SNAP and SNAG res ulted in 85% inhibition of FGF2-induced neovascularization in the mouse Mat rigel model when given at 5 mg/kg/day infusion in minipumps during 14 days and 87% inhibition of angiogenesis induced by FGF2 in the CAM when administ ered a single dose of 50 mug. Thus, NO donors might be a useful tool for th e inhibition of angiogenesis associated with human tumor growth, or neovasc ular, ocular, and inflammatory diseases. (C) 2000 Wiley-Liss, Inc.