Skip to main content

Mouse aortic ring assay: A new approach of the molecular genetics of angiogenesis


Angiogenesis, a key step in many physiological and pathological processes, involves proteolysis of the extracellular matrix. To study the role of two enzymatic families, serine-proteases and matrix metalloproteases in angiogenesis, we have adapted to the mouse, the aortic ring assay initially developed in the rat. The use of deficient mice allowed us to demonstrate that PAI-1 is essential for angiogenesis while the absence of an MMP, MMP-11, did not affect vessel sprouting. We report here that this model is attractive to elucidate the cellular and molecular mechanisms of angiogenesis, to identify, characterise or screen “pro- or anti-angiogenic agents that could be used for the treatment of angiogenesis-dependent diseases. Approaches include using recombinant proteins, synthetic molecules and adenovirus-mediated gene transfer.


  1. 1.

    Folkman J. Toward an understanding of angiogenesis: search and discovery. Perspect Biol Med 1985;29:10–36.

    PubMed  CAS  Google Scholar 

  2. 2.

    Passaniti A, Taylor RM, Pili R, Guo Y, Long PV, Haney JA, Pauly RR, Grant DS, Martin GR. A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor. Lab Invest 1992;67:519–528.

    PubMed  CAS  Google Scholar 

  3. 3.

    McMahon GA, Petitclerc E, Stefansson S, Smith E, Wong MK, Westrick RJ, Ginsburg D, Brooks PC, Lawrence DA. Plasminogen activator inhibitor-1 regulates tumor growth and angiogenesis. J Biol Chem 2001;276:33964–33968.

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Nicosia RF, Ottinetti A. Growth of microvessels in serum-free matrix culture of rat aorta. A quantitative assay of angiogenesis in vitro. Lab Invest 1990;63:115–122.

    PubMed  CAS  Google Scholar 

  5. 5.

    Carmeliet P, Collen D. Transgenic mouse models in angiogenesis and cardiovascular disease. J Pathol 2000;190:387–405.

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Jos Jonkers and Anton Berns. Conditional mouse models of sporadic cancer. Nature Reviews/Cancer 2, 251–265. 2002. Ref Type: Generic

    CAS  Google Scholar 

  7. 7.

    Reynolds LE, Wyder L, Lively JC, Taverna D, Robinson SD, Huang X, Sheppard D, Hynes RO, Hodivala-Dilke KM. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med 2002;8:27–34.

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Bajou K, Noel A, Gerard RD, Masson V, Brunner N, Holst-Hansen C, Skobe M, Fusenig NE, Carmeliet P, Collen D, Foidart JM. Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nat Med 1998;4:923–928.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Bajou K, Masson V, Gerard RD, Schmitt PM, Albert V, Praus M, Lund LR, Frandsen TL, Brunner N, Dano K, Fusenig NE, Weidle U, Carmeliet G, Loskutoff D, Collen D, Carmeliet P, Foidart JM, Noel A. The plasminogen activator inhibitor PAI-1 controls in vivo tumor vascularization by interaction with proteases, not vitronectin. Implications for antiangiogenic strategies. J Cell Biol 2001;152:777–784.

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Pepper MS. Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol 2001;21:1104–1117.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Mikala Egeblad and Zena Werb. New functions for the matrix metalloproteinases in cancer progression. Nature Reviews/Cancer 2, 163–176. 2002. Ref Type: Generic

    Article  CAS  Google Scholar 

  12. 12.

    Devy L, Blacher S, Grignet-Debrus C, Bajou K, Masson V, Gerard RD, Gils A, Carmeliet G, Carmeliet P, Declerck PJ, Noel A, Foidart JM. The pro- or antiangiogenic effect of plasminogen activator inhibitor 1 is dose dependent. FASEB J 2002;16:147–154.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Lambert V, Munaut C, Noel A, Frankenne F, Bajou K, Gerard R, Carmeliet P, Defresne MP, Foidart JM, Rakic JM. Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization. FASEB J 2001;15:1021–1027.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Masson R, Lefebvre O, Noel A, Fahime ME, Chenard MP, Wendling C, Kebers F, LeMeur M, Dierich A, Foidart JM, Basset P, Rio MC. In vivo evidence that the stromelysin-3 metalloproteinase contributes in a paracrine manner to epithelial cell malignancy. J Cell Biol 1998;140:1535–1541.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Montesano R, Orci L, Vassalli P. In vitro rapid organization of endothelial cells into capillary-like networks is promoted by collagen matrices. J Cell Biol 1983;97:1648–1652.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Blacher S, Devy L, Burbridge MF, Roland G, Tucker G, Noel A, Foidart JM. Improved quantification of angiogenesis in the rat aortic ring assay. Angiogenesis 2001;4:133–142.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Voyta JC, Via DP, Butterfield CE, Zetter BR. Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein. J Cell Biol 1984;99:2034–2040.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Li H, Lu H, Griscelli F, Opolon P, Sun LQ, Ragot T, Legrand Y, Belin D, Soria J, Soria C, Perricaudet M, Yeh P. Adenovirus-mediated delivery of a uPA/uPAR antagonist suppresses angiogenesis-dependent tumor growth and dissemination in mice. Gene Ther 1998;5:1105–1113.

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Zhu WH, Guo X, Villaschi S, Francesco NR. Regulation of vascular growth and regression by matrix metalloproteinases in the rat aorta model of angiogenesis. Lab Invest 2000;80:545–555.

    PubMed  CAS  Google Scholar 

  20. 20.

    Noel AC, Lefebvre O, Maquoi E, VanHoorde L, Chenard MP, Mareel M, Foidart JM, Basset P, Rio MC. Stromelysin-3 expression promotes tumor take in nude mice. J Clin Invest 1996;97:1924–1930.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Sounni NE, Devy L, Hajitou A, Frankenne F, Munaut C, Gilles C, Deroanne C, Thompson EW, Foidart JM, Noel A. MT1-MMP expression promotes tumor growth and angiogenesis through an up- regulation of vascular endothelial growth factor expression. FASEB J 2002;16:555–564.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Sounni NE, Baramova EN, Munaut C, Maquoi E, Frankenne F, Foidart JM, Noel A. Expression of membrane type 1 matrix metalloproteinase (MT1-MMP) in A2058 melanoma cells is associated with MMP-2 activation and increased tumor growth and vascularization. Int J Cancer 2002;98:23–28.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Mazar AP. The urokinase plasminogen activator receptor (uPAR) as a target for the diagnosis and therapy of cancer. Anticancer Drugs 2001;12:387–400.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information



Corresponding authors

Correspondence to Véronique Masson or Agnès Noël.

Additional information

Published: October 28, 2002

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Masson, V., Devy, L., Grignet-Debrus, C. et al. Mouse aortic ring assay: A new approach of the molecular genetics of angiogenesis. Biol Proced Online 4, 24 (2002).

Download citation

Indexing terms

  • Angiogenesis factor
  • endothelium
  • transgenic
  • mice
  • recombinant adenovirus