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-1 alpha (HIF-1 alpha) under different hypoxic conditions (3% and nearly 0% O-2) and Co2+-concentrations (0.01-0.7 mM). As in hypoxia, the amount of HIF-1 alpha 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 (>= 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.