Paradoxical effects of hypoxia-mimicking divalent cobalt ions in human endothelial cells in vitro

Divalent cobalt ions (Co2+) induce the expression of hypoxia responsive genes and are often used in cell biology to mimic hypoxia. In this in vitro study we compared the effects of hypoxia and Co2+ on human endothelial cells and examined processes that are stimulated in hypoxia in vivo (proliferation and angiogenesis). We analyzed the expression of the hypoxia-inducible factor-1alpha (HIF-1alpha) under different hypoxic conditions (3% and nearly 0% O2) and Co2+ -concentrations (0.01-0.7 mM). As in hypoxia, the amount of HIF-1alpha protein was enhanced by exposure to Co2+ (did not correlate with mRNA amount). however, contrary to the results of hypoxia, in vitro-angiogenesis was inhibited after exposure to even low Co2+-concentrations (> or =0.01 mM). This led to the conclusion that although hypoxia signaling after Co2+ -exposure took place, further yet unknown Co2+ -induced event(s) must have occurred.