TY - JOUR
T1 - Hypoxia-induced endothelial progenitor cell function is blunted in angiotensinogen knockout mice
AU - Choi, Jin Hwa
AU - Nguyen, Minh Phuong
AU - Lee, Dongjin
AU - Oh, Goo Taeg
AU - Lee, You Mie
PY - 2014/6
Y1 - 2014/6
N2 - 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)-1α and -2α 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-1α 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.
AB - 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)-1α and -2α 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-1α 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.
KW - Angiotensinogen
KW - Endothelial progenitor cell
KW - Hypertension
KW - Tumor
KW - Vasculogenesis
UR - http://www.scopus.com/inward/record.url?scp=84903900068&partnerID=8YFLogxK
U2 - 10.14348/molcells.2014.0119
DO - 10.14348/molcells.2014.0119
M3 - Article
C2 - 24938229
AN - SCOPUS:84903900068
SN - 1016-8478
VL - 37
SP - 487
EP - 496
JO - Molecules and Cells
JF - Molecules and Cells
IS - 6
ER -