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Role of arginase‐I in VEGF‐induced capillary‐like tube formation
Author(s) -
Li Zhenbo,
Hein Travis W.,
Kuo Lih
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a529-b
Subject(s) - arginase , angiogenesis , umbilical vein , vascular endothelial growth factor , chemistry , nitric oxide , snap , microbiology and biotechnology , ornithine , biology , biochemistry , vegf receptors , arginine , cancer research , in vitro , computer graphics (images) , organic chemistry , amino acid , computer science
Accumulating evidence suggests that arginase, a key enzyme for ornithine production and polyamine synthesis, is increased in angiogenesis‐associated disorders. However, the relationship between arginase and vascular endothelial growth factor (VEGF) in angiogenesis remains unclear. The present study was designed to investigate the role of arginase‐I (AI) in VEGF‐induced capillary‐like endothelial tube formation. Both VEGF (50 ng/ml) and nitric oxide (NO) donor, S‐nitroso‐N‐acetylpenicillamine (SNAP; 0.1 mM), increased AI expression and enhanced capillary‐like tube formation in human umbilical vein endothelial cells (HUVEC). Inhibition of arginase activity by N ω ‐hydroxy‐nor‐L‐arginine (nor‐NOHA, 0.1 mM) reduced capillary‐like tube formation in response to VEGF and to SNAP. Over‐expression of AI with an adenoviral vector in HUVEC promoted tube formation and enhanced activation of hypoxia‐inducible factor (HIF)‐1α and NF‐κB as determined by a gel shift assay. Likewise, nor‐NOHA eliminated the angiogenic effect of over‐expressed AI and decreased the activation of these transcription factors. It is concluded that AI, being at the downstream pathway of NO, plays a key role in VEGF‐induced tube formation by activating HIF‐1α and NF‐κB. The present results provide a novel signal pathway for VEGF‐induced angiogenesis. HL‐71761 to LK