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Hydrogen Peroxide Induces Vascular Permeability via Regulation of Vascular Endothelial Growth Factor

Department of Internal Medicine, Airway Remodeling Laboratory, Research Center for Allergic Immune Diseases, and Department of Radiology, Chonbuk National University Medical School, Jeonju, South Korea

Correspondence and requests for reprints should be addressed to Yong Chul Lee, M.D., Ph.D., Department of Internal Medicine, Chonbuk National University Medical School, San 2-20 Geumam-dong, deokjin-gu, Jeonju, Jeonbuk 561-180, South Korea. E-mail: leeyc{at}chonbuk.ac.kr

Oxidative stress plays critical roles in initiation and/or worsening of respiratory disease process. Although reactive oxygen species (ROS) are shown to cause vascular leakage, the mechanisms by which ROS induce an increase in vascular permeability are not clearly understood. In this study, we have used a murine model to evaluate the effect of hydrogen peroxide (H₂O₂) to examine roles of ROS and the molecular mechanism in vascular permeability. The results have revealed that ROS levels, vascular endothelial growth factor (VEGF) expression, hypoxia-inducible factor-1 protein level, airway hyperresponsiveness, and vascular permeability are increased after inhalation of H₂O₂. Administration of antioxidants markedly reduced plasma extravasation and VEGF levels in lungs treated with H₂O₂. These results indicate that ROS may modulate vascular permeability via upregulation of VEGF expression.

Key Words: airway • animal model • hydrogen peroxide • reactive oxygen species • vascular permeability • vascular endothelial growth factor