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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis.

Angiopoietin-1 ( Ang1) mediates angiogenesis by enhancing endothelial cell survival and migration. It is also known that Ang1 activates Tie2, an endothelial-specific tyrosine kinase receptor, but the molecular mechanism of this process is not clear. In this study, we investigated whether reactive oxygen species (ROS) production plays a role in Ang1-mediated angiogenesis. We found that human umbilical vein endothelial cells treated with Ang1 produce ROS transiently, which was suppressed by NADPH oxidase inhibitor, diphenylene-iodonium chloride, and rotenone. The Ang1-induced ROS was identified as hydrogen peroxide (H2O2) using adenovirus-catalase infection. Removal of H2O2 by adenovirus-catalase significantly suppressed Ang1-induced in vitro endothelial cell migration, in vivo tubule formation and angiogenesis, and activation of p44/42 mitogen-activated protein kinase ( MAPK), involved in cell migration, and delayed the deactivation of Akt phosphorylation involved in cell survival. Supporting to in vitro data, Ang1- induced vascular remodeling in catalase (-/-) mice was more prominent than in catalase (+/+) mice: Ang1- induced increases of the diameter of terminal arterioles and the postcapillary venules in catalase (-/-) mice were significant compared with catalase (+/+) mice. These results show that Ang1- induced H2O2 plays an important role in Ang1- mediated angiogenesis by modulating p44/42 MAPK activity.[1]


  1. Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis. Kim, Y.M., Kim, K.E., Koh, G.Y., Ho, Y.S., Lee, K.J. Cancer Res. (2006) [Pubmed]
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