Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis

Young Mee Kim, Kyung Eun Kim, Gou Young Koh, Ye Shih Ho, Kong Joo Lee

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76 Scopus citations


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, diphenyleneiodonium 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.

Original languageEnglish (US)
Pages (from-to)6167-6174
Number of pages8
JournalCancer Research
Issue number12
StatePublished - Jun 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kim, Y. M., Kim, K. E., Koh, G. Y., Ho, Y. S., & Lee, K. J. (2006). Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis. Cancer Research, 66(12), 6167-6174. https://doi.org/10.1158/0008-5472.CAN-05-3640