Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Hypoxia-Induced Endothelial Progenitor Cell Function Is Blunted in Angiotensinogen Knockout Mice

  • Choi, Jin-Hwa (National Basic Research Laboratory of Vascular Homeostasis Regulation, College of Pharmacy, Kyungpook National University) ;
  • Nguyen, Minh-Phuong (National Basic Research Laboratory of Vascular Homeostasis Regulation, College of Pharmacy, Kyungpook National University) ;
  • Lee, Dongjin (National Basic Research Laboratory of Vascular Homeostasis Regulation, College of Pharmacy, Kyungpook National University) ;
  • Oh, Goo-Taeg (Department of Life Science, Ewha University) ;
  • Lee, You-Mie (National Basic Research Laboratory of Vascular Homeostasis Regulation, College of Pharmacy, Kyungpook National University)
  • Received : 2014.05.09
  • Accepted : 2014.06.05
  • Published : 2014.06.30
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Abstract

Angiotensinogen (AGT), the precursor of angiotensin I, is known to be involved in tumor angiogenesis and associated with the pathogenesis of coronary atherosclerosis. This study was undertaken to determine the role played by AGT in endothelial progenitor cells (EPCs) in tumor progression and metastasis. It was found that the number of EPC colonies formed by AGT heterozygous knockout ($AGT^{+/-}$) cells was less than that formed by wild-type (WT) cells, and that the migration and tube formation abilities of $AGT^{+/-}$ EPCs were significantly lower than those of WT EPCs. In addition, the gene expressions of vascular endothelial growth factor (VEGF), Flk1, angiopoietin (Ang)-1, Ang-2, Tie-2, stromal derived factor (SDF)-1, C-X-C chemokine receptor type 4 (CXCR4), and of endothelial nitric oxide synthase (eNOS) were suppressed in $AGT^{+/-}$ EPCs. Furthermore, the expressions of hypoxia-inducible factor (HIF)-$1{\alpha}$and $-2{\alpha}$ were downregulated in $AGT^{+/-}$ early EPCs under hypoxic conditions, suggesting a blunting of response to hypoxia. Moreover, the activation of Akt/eNOS signaling pathways induced by VEGF, epithelial growth factor (EGF), or SDF-$1{\alpha}$ were suppressed in $AGT^{+/-}$ EPCs. In $AGT^{+/-}$ mice, the incorporation of EPCs into the tumor vasculature was significantly reduced, and lung tumor growth and melanoma metastasis were attenuated. In conclusion, AGT is required for hypoxia-induced vasculogenesis.

Keywords

References

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