Skip to main content

Evaluation of VEGF-Induced Vascular Permeability in Mice

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 763))

Abstract

Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis and vascular leak involved in development, wound healing, tumor growth, macular degeneration, and ischemia. Studying the effects of VEGF in vitro is not always sufficient to approximate the complex in vivo response that involves multiple cell types within functioning tissues. Treating mice with an intravenous injection of recombinant VEGF produces a rapid and transient biochemical response that is accompanied by a series of ultrastructural changes. Similar events are induced by hypoxia-induced VEGF in the heart following myocardial infarction or by tumor cell-released VEGF during metastasis. Studying how intact blood vessels respond to VEGF will augment the further development of antipermeability strategies to improve disease progression in a number of pathologies.

This is a preview of subscription content, log in via an institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Senger, D. R., Galli, S. J., Dvorak, A. M., Perruzzi, C. A., Harvey, V. S., and Dvorak, H. F. (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid, Science 219, 983–985.

    Article  PubMed  CAS  Google Scholar 

  2. Ferrara, N., Hillan, K. J., and Novotny, W. (2005) Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy, Biochem Biophys Res Commun 333, 328–335.

    Article  PubMed  CAS  Google Scholar 

  3. Rosina, C., Bottoni, F., and Staurenghi, G. (2008) Clinical experience with pegaptanib sodium, Clin Ophthalmol 2, 485–488.

    PubMed  CAS  Google Scholar 

  4. Weis, S., Cui, J., Barnes, L., and Cheresh, D. (2004) Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis, J Cell Biol 167, 223–229.

    Article  PubMed  CAS  Google Scholar 

  5. Weis, S., Shintani, S., Weber, A., Kirchmair, R., Wood, M., Cravens, A., McSharry, H., Iwakura, A., Yoon, Y. S., Himes, N., Burstein, D., Doukas, J., Soll, R., Losordo, D., and Cheresh, D. (2004) Src blockade stabilizes a Flk/cadherin complex, reducing edema and tissue injury following myocardial infarction, J Clin Invest 113, 885–894.

    PubMed  CAS  Google Scholar 

  6. Eliceiri, B. P., Paul, R., Schwartzberg, P. L., Hood, J. D., Leng, J., and Cheresh, D. A. (1999) Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability, Mol Cell 4, 915–924.

    Article  PubMed  CAS  Google Scholar 

  7. Boschelli, D. H., Ye, F., Wang, Y. D., Dutia, M., Johnson, S. L., Wu, B., Miller, K., Powell, D. W., Yaczko, D., Young, M., Tischler, M., Arndt, K., Discafani, C., Etienne, C., Gibbons, J., Grod, J., Lucas, J., Weber, J. M., and Boschelli, F. (2001) Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity, J Med Chem 44, 3965–3977.

    Article  PubMed  CAS  Google Scholar 

  8. Golas, J. M., Arndt, K., Etienne, C., Lucas, J., Nardin, D., Gibbons, J., Frost, P., Ye, F., Boschelli, D. H., and Boschelli, F. (2003) SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice, Cancer Res 63, 375–381.

    PubMed  CAS  Google Scholar 

  9. Rogers, M. S., Rohan, R. M., Birsner, A. E., and D’Amato, R. J. (2003) Genetic loci that control vascular endothelial growth factor-induced angiogenesis, Faseb J 17, 2112–2114.

    PubMed  CAS  Google Scholar 

  10. Chan, C. K., Pham, L. N., Zhou, J., Spee, C., Ryan, S. J., and Hinton, D. R. (2005) Differential expression of pro- and antiangiogenic factors in mouse strain-dependent hypoxia-induced retinal neovascularization, Lab Invest 85, 721.

    Article  PubMed  CAS  Google Scholar 

  11. Potter, M. D., Barbero, S., and Cheresh, D. A. (2005) Tyrosine phosphorylation of VE-cadherin prevents binding of p120- and beta-catenin and maintains the cellular mesenchymal state, J Biol Chem 280, 31906–31912.

    Article  PubMed  CAS  Google Scholar 

  12. Weis, S. M., Lindquist, J. N., Barnes, L. A., Lutu-Fuga, K. M., Cui, J., Wood, M. R., and Cheresh, D. A. (2007) Cooperation between VEGF and beta3 integrin during cardiac vascular development, Blood 109, 1962–1970.

    Article  PubMed  CAS  Google Scholar 

  13. Weis, S. M., and Cheresh, D. A. (2005) Pathophysiological consequences of VEGF-induced vascular permeability, Nature 437, 497–504.

    Article  PubMed  CAS  Google Scholar 

  14. Mendelsohn, M. E., and Karas, R. H. (2005) Molecular and Cellular Basis of Cardiovascular Gender Differences, Science 308, 1583–1587.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The methods described here were developed in the lab of David Cheresh formerly at The Scripps Research Institute in La Jolla and now at the University of California San Diego. The author would like to thank Dr. Cheresh as well as past and present members of the Cheresh lab for their contribution to these projects. The ultrastructural work would not have been possible without the technical expertise of Dr. Malcolm Wood at the TSRI Electron Microscopy Core.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sara M. Weis .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Weis, S.M. (2011). Evaluation of VEGF-Induced Vascular Permeability in Mice. In: Turksen, K. (eds) Permeability Barrier. Methods in Molecular Biology, vol 763. Humana Press. https://doi.org/10.1007/978-1-61779-191-8_27

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-191-8_27

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-190-1

  • Online ISBN: 978-1-61779-191-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics