DOI: 10.1073/pnas.041359198. Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability [Penn]

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

10.1073/pnas.041359198

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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 .

Bibliography

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, 98(5), 2604â2609.

Authors 9

Dai Fukumura (first)
Takeshi Gohongi (additional)
Ananth Kadambi (additional)
Yotaro Izumi (additional)
Jennifer Ang (additional)
Chae-Ok Yun (additional)
Donald G. Buerk (additional)
Paul L. Huang (additional)
Rakesh K. Jain (additional)

References 44 Referenced 825

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:45 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 12:39 p.m.)
Indexed	1 day, 11 hours ago (Sept. 3, 2025, 7:06 a.m.)
Issued	24 years, 6 months ago (Feb. 27, 2001)
Published	24 years, 6 months ago (Feb. 27, 2001)
Published Online	24 years, 6 months ago (Feb. 27, 2001)
Published Print	24 years, 6 months ago (Feb. 27, 2001)

Funders 0

None

BibTeX

@article{Fukumura_2001, title={Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.041359198}, DOI={10.1073/pnas.041359198}, number={5}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Fukumura, Dai and Gohongi, Takeshi and Kadambi, Ananth and Izumi, Yotaro and Ang, Jennifer and Yun, Chae-Ok and Buerk, Donald G. and Huang, Paul L. and Jain, Rakesh K.}, year={2001}, month=feb, pages={2604–2609} }

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    },
    {
      "value": "2001-02-27",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}