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

Open access
Fukumura, Dai, Gohongi, Takeshi, Kadambi, Ananth, Izumi, Yotaro, Ang, Jennifer, Yun, Chae-Ok, Buerk, Donald G., Huang, Paul L., Jain, Rakesh K.·2001·Proceedings of the National Academy of Sciences

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 - N 6 -(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 .

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Metadata

Authors
Fukumura, D., Gohongi, T., Kadambi, A., Izumi, Y., Ang, J., Yun, C.-O., Buerk, D. G., Huang, P. L., & Jain, R. K.
Venue
Proceedings of the National Academy of Sciences
Published
2001-02-27
Volume
98
Issue
5
Pages
2604-2609
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1968719918
Cited by
1,020
References
45
FWCI
12.27
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability. https://app.cochat.ai/papers/10.1073/pnas.041359198
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Fukumura, D., Gohongi, T., Kadambi, A., Izumi, Y., Ang, J., Yun, C.-O., Buerk, D. G., Huang, P. L., & Jain, R. K. (2001). Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.041359198

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