Vascular endothelial growth factor (VEGF) is an endothelial-specific growth factor that activates the small GTPase RhoA. While the role of RhoA for VEGF-driven endothelial migration and angiogenesis has been studied in detail, the function of its target proteins, the Rho-dependent kinases ROCK I and II, are controversially discussed. Using the mouse model of oxygen-induced proliferative retinopathy, ROCK I/II inhibition by H-1152 resulted in increased angiogenesis. This enhanced angiogenesis, however, was completely blocked by the VEGF-receptor antagonist PTK787/ZK222584. Loss-of-function experiments in endothelial cells revealed that inhibition of ROCK I/II using the pharmacological inhibitor H-1152 and ROCK I/II-specific small-interfering RNAs resulted in a rise of VEGF-driven sprouting angiogenesis. These functional data were biochemically substantiated by showing an enhanced VEGF-receptor kinase insert domain receptor phosphorylation and extracellular signal-regulated kinase 1/2 activation after inhibition of ROCK I/II. Thus our data identify that the inhibition of Rho-dependent kinases ROCK I/II activates angiogenesis both, in vitro and in vivo.

Metal oxides may hold, as nanosized particles, a toxic potential to human health and the environment that is not present in the bulk material. Due to the high surface-to-volume ratio, small amounts can lead to strong oxidative damage within biological systems, impairing cellularfunctions as a consequence of their high surface reactivity. We report here on a new nanosized V203 material that has a needle-like structure with diameters of less than 30 nm and variable lengths. The potentiated toxicity of nanoscale vanadium oxide (V203) compared to bulk material is demonstrated here in human endo- and epithelial lung cells, and might be due to the higher catalytic surface of the particles. Reduction in cell viability is almost ten times stronger and starts with lowest concentrations of "nanoscaled" material (10 microg/mL). Vanadium oxide leads to an induction of heme oxygenase 1 (HO-1) in a dose dependent manner in ECV304 cells whereas a reduction in protein levels can be observed for the epithelial cells (A549). Lipid peroxidation can be observed also for "nanoscaled" vanadium oxide to a much stronger extent in macrophages (RAW cells) than for bulk material. The observed effects can not only be explained by oxidation from V2O3 to V2O5 as there are significant differences between the novel nano vanadium and all used bulk materials (V203 and V205). It appears rather to be a nanoeffect of a high surface reactivity, here coupled with a yet unknown toxicity potentiating effect of a technically important catalyst.

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The sections in this article are Introduction Nanoscale Materials and Adverse Health Effects: Precautionary Measures Hazard Identification and Exposure Estimation Production and Use of “New Carbon Modifications” and Metal Oxides Health Aspects Uptake and Possible Transport, Depots, and Accumulation in Living Organisms Biological Effects on Cellular Mechanisms Metal Oxides New Carbon Modifications Possible Hazards – Toxicological Impacts Risk Characterization – A Conclusion Opportunities and Risks of Nanomaterials New Materials without Risks?

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