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Predominant role of endothelial nitric oxide synthase in VEGF-induced angiogenesis and vascular permeability

Authors
 Dai Fukumura  ;  Takeshi Gohongi  ;  Ananth Kadambi  ;  Yotaro Izumi  ;  Jennifer Ang  ;  Chae-Ok Yun  ;  Donald G. Buerk  ;  Paul L. Huang  ;  Rakesh K. Jain 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.98(5) : 2604-2609, 2001 
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN
 0027-8424 
Issue Date
2001
MeSH
Animals ; Blood Circulation/physiology ; Capillary Permeability/physiology* ; Endothelial Growth Factors/physiology* ; Female ; Homeodomain Proteins/genetics ; Homeodomain Proteins/physiology ; Lymphokines/physiology* ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neovascularization, Physiologic/physiology* ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/genetics ; Nitric Oxide Synthase/physiology* ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase Type III ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
Abstract
Nitric oxide (NO) plays a critical role in vascular endothelial growth factor (VEGF)-induced angiogenesis and vascular hyperpermeability. However, the relative contribution of different NO synthase (NOS) isoforms to these processes is not known. Here, we evaluated the relative contributions of endothelial and inducible NOS (eNOS and iNOS, respectively) to angiogenesis and permeability of VEGF-induced angiogenic vessels. The contribution of eNOS was assessed by using an eNOS-deficient mouse, and iNOS contribution was assessed by using a selective inhibitor [l-N6-(1-iminoethyl) lysine, l-NIL] and an iNOS-deficient mouse. Angiogenesis was induced by VEGF in type I collagen gels placed in the mouse cranial window. Angiogenesis, vessel diameter, blood flow rate, and vascular permeability were proportional to NO levels measured with microelectrodes: Wild-type (WT) ≥ WT with l-NIL or iNOS−/− > eNOS−/− ≥ eNOS−/− with l-NIL. The role of NOS in VEGF-induced acute vascular permeability increase in quiescent vessels also was determined by using eNOS- and iNOS-deficient mice. VEGF superfusion significantly increased permeability in both WT and iNOS−/− mice but not in eNOS−/− mice. These findings suggest that eNOS plays a predominant role in VEGF-induced angiogenesis and vascular permeability. Thus, selective modulation of eNOS activity is a promising strategy for altering angiogenesis and vascular permeability in vivo.
Files in This Item:
T200103668.pdf Download
DOI
10.1073/pnas.041359198
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
Yonsei Authors
Yun, Chae Ok(윤채옥)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/143052
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