The Extracellular Matrix as a Modulator of Angiogenesis

  • Joseph A. Madri
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Endothelium is comprised of heterogeneous cell populations residing in a variety of vascular beds. The endothelial cells resident in these diverse vascular beds or regions exhibit a broad range of diversity in their functions and appearances in addition to their shared common features such as non-thrombogenicity, polarity, and transport functions. Response to injury (neovascularization) is a response common to all endothelial cell populations, yet the responses vary depending on whether the endothelial cells are derived from large vessels or the microvasculature. Another factor thought to play an important role in the modulation of endothelial cell behavior in response to injury is the extracellular matrix. Large-vessel endothelial cells respond to injury by sheet migration/proliferation until the defect is covered. Evidence has been accrued supporting the concept that the underlying matrix determines, in part, the migration and proliferation rates, possibly via modulating cytoskeletal organization of the cells. In addition, the continual synthesis and secretion of matrix components by the responding cells appear to be crucial in the response to injury. Although microvascular endothelial cells respond to injury by migration and proliferation as do the large vessel endothelial cells, they migrate through interstitial tissue and ultimately form capillaries. Recent evidence has demonstrated that matrix composition can affect proliferation rate, matrix synthesis, and multicellular organization during the neovascularization process. In addition, matrix organization appears to influence differentiation of microvascular endothelial cells, specifically the ability of selected endothelial cell populations to form fenestrations. Thus, matrix composition and organization appear to play significant roles in orchestrating the growth and differentiation of endothelial cells during the highly integrated series of responses known as neovascularization.


Endothelial Cell Basement Membrane Microvascular Endothelial Cell Aortic Endothelial Cell Bovine Aortic Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Bissell, M. L., Hall, H. G., and Parry, G., 1982, How does the extracellular matrix direct gene expression? J. Theor. Biol. 99:31–68.PubMedCrossRefGoogle Scholar
  2. Fishman, A. P. (ed.), 1982, Endothelium ,New York Academy of Sciences, New York.Google Scholar
  3. Fleischmajer, R., Olsen, B. R., and Kuhn, K. (eds.), 1986, Biology, Chemistry and Pathology of Collagen ,New York Academy of Sciences, New York.Google Scholar
  4. Form, D. M., and Madri, J. A., 1985, Proliferation of microvascular endothelial cells in vitro Modulation by extracellular matrix, Fed. Proc. 44:7309.Google Scholar
  5. Form, D. J., Pratt, B. M., and Madri, J. A., 1986, Endothelial cell proliferation during angiogenesis: In vitro modulation by basement membrane components. Lab. Invest. 55:521–530.PubMedGoogle Scholar
  6. Gotlieb, A. I., Spector, W., Wong, M. K. K., and Lacey, C., 1984a, In vitro reendothelialization: Microfilament bundle reorganization in migrating porcine endothelial cells, Arteriosclerosis 4:91–96.PubMedCrossRefGoogle Scholar
  7. Gotlieb, A. I., Subrahmanyan, L., and Kalnins, V. I., 1984b, Microtubule-organizing centers and cell migration: Effect of inhibition of migration and microtubule disruption in endothelial cells, J. Cell Biol. 96:1266–1272.CrossRefGoogle Scholar
  8. Herman, I. M., Pollard, T. D., and Wong, A. J., 1982, Contractile proteins in endothelial cells, Ann. N.Y. Acad. Sci. 401:50–60.PubMedCrossRefGoogle Scholar
  9. Ingber, D. E., Madri, J. A., and Jamieson, J. D., 1981, Role of basal lamina in neoplastic disorganization of tissue architecture, Proc. Natl. Acad. Sci. U.S.A. 78:3901–3905.PubMedCrossRefGoogle Scholar
  10. Ingber, D. E., Madri, J. A., and Jamieson, J. D., 1985, Neoplastic disorganization of pancreatic epithelial cell-cell relations, Am. J. Pathol. 121:248–260.PubMedGoogle Scholar
  11. Ingber, D. E., Madri, J. A., and Jamieson, J. D., 1986, Basement membrane as a spacial organizer of polarized epithelia: Exogenous basement membrane reorients pancreatic epithelial tumor cells, Am. J. Pathol. 122:129–139.PubMedGoogle Scholar
  12. Kurkinen, M., Taylor, A., Garrels, A., and Hogan, B. M. L., 1984, Cell-surface-associated proteins which bind native type IV collagen and gelatin, J. Biol. Chem. 259:5915–5922.PubMedGoogle Scholar
  13. Leto, T. L., Pratt, B. M., and Madri, J. A., 1986, Mechanisms of cytoskeletal regulation: Modulation of aortic endothelial cell protein band 4.1 by extracellular matrix, J. Cell Physiol. 127:423–431.PubMedCrossRefGoogle Scholar
  14. Lwebuga-Mukasa, J., Thulin, G., Madri, J. A., Barrett, C., and Warshaw, J., 1984, An acellular human amnion membrane model for in vitro culture of type II pneumocytes: The role of the basement membrane on cell morphology and function, J. Cell. Physiol. 121:215–225.PubMedCrossRefGoogle Scholar
  15. Lwebuga-Mukasa, J., Ingbar, D. H., and Madri, J. A., 1986, Repopulation of a human alveolar matrix by adult rat type II pneumocytes in vitro, Exp. Cell Res. 162:423–435.PubMedCrossRefGoogle Scholar
  16. Madri, J. A., 1982, Endothelial cell-matrix interactions in hemostasis, in: Progress in Hemostasis and Thrombosis ,Vol. 6 (T. H. Spaet, ed.), Grune & Stratton, New York, pp. 1–24.Google Scholar
  17. Madri, J. A., and Stenn, K. S., 1982, Aortic endothelial cell migration. I. Matrix requirements and composition, Am. J. Pathol. 106:180–186.PubMedGoogle Scholar
  18. Madri, J. A., and Pratt, B. M., 1986, Endothelial cell-matrix interactions: In vitro models of angi-ogenesis, J. Histochem. Cytochem. 34:85–91.PubMedCrossRefGoogle Scholar
  19. Madri, J. A., and Pratt, B. M., 1987, Angiogenesis, in: The Molecular and Cellular Biology of Wound Repair ,(R. A. Clark and P. Henson, eds.), Plenum Press, New York (in press).Google Scholar
  20. Madri, J. A., and Williams, S. K., 1983, Capillary endothelial cell cultures: Phenotypic modulation by matrix components, J. Cell Biol. 97:153–165.PubMedCrossRefGoogle Scholar
  21. Montesano, R. L., Orci, L., and Vassali, P., 1983, In vitro rapid organization of endothelial cells into capillary-like networks is promoted by collagen matrices, J. Cell Biol. 97:1648–1652.PubMedCrossRefGoogle Scholar
  22. Palotie, A., Tryggvason, K., Peltonen, L., and Seppa, H., 1983, Components of the subendothelial aorta basement membrane. Immunohistochemical localization and role in cell attachment, Lab. Invest. 49:362–372.PubMedGoogle Scholar
  23. Pratt, B. M., Harris, A. S., Morrow, J. S., and Madri, J. A., 1984, Mechanisms of cytoskeletal regulation: Modulation of aortic endothelial cell spectrin by the extracellular matrix. Am. J. Pathol. 117:348–354.Google Scholar
  24. Pratt, B. M., Form, D., and Madri, J. A., 1986, Endothelial cell-extracellular matrix interactions, Ann. N.Y. Acad. Sci. 460:274–288.CrossRefGoogle Scholar
  25. Pytela, R., Pierschbacher, M. D., and Ruoslahti, E., 1985, Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor Cell 40:191–198.PubMedCrossRefGoogle Scholar
  26. von der Mark, K., and Kuhl, U., 1985, Laminin and its receptor, Biochim. Biophys. Acta 823:147–160.PubMedGoogle Scholar
  27. Yannariello-Brown, J., and Madri, J. A., 1985, Aortic endothelial cells synthesize specific binding proteins for laminin and type IV collagen, J. Cell Biol. 101:333a.Google Scholar
  28. Yannariello-Brown, J., Tchao, N., Liotta, L., and Madri, J. A., 1985, Co-distribution of the laminin receptor with actin microfilaments in permeablized aortic and microvascular endothelial cells, J. Cell Biol. 101:333a.Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Joseph A. Madri
    • 1
  1. 1.Department of PathologyYale University School of MedicineNew HavenUSA

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