The role of plasminogen in angiogenesis in vivo

J Thromb Haemost. 2003 Aug;1(8):1683-7. doi: 10.1046/j.1538-7836.2003.00182.x.

Abstract

Plasminogen, by virtue of its role in the degradation of extracellular matrix proteins and by facilitation of cell migration, may contribute to angiogenesis.

Objective: the purpose of this study was to evaluate the contribution of plasminogen to angiogenesis in vivo.

Methods: Angiogenesis was assessed in gene-targeted mice with deficiencies of plasminogen, urokinase plasminogen activator (uPA), and urokinase receptor (uPAR) in a mouse corneal model. In wild-type mice, female and young mice showed a trend toward increased angiogenesis compared to males and old mice. Because of this influence of age and gender on angiogenesis, young, female mice (6-13 weeks of age) were used for this study.

Results: In response to angiogenic stimulation by basic fibroblast growth factor (bFGF), uPA deficient mice exhibited a decrease in new vessel formation as reflected by vessel length (0.47 in control vs. 0.33 mm in uPA-/- mice, P = 0.043), but new vessel formation was not altered (P = 0.107) in the uPAR deficient mice compared to control mice. A significantly decreased angiogenic response of new vessel formation to both vascular endothelial growth factor (VEGF) (P < 0.02) and bFGF (P < 0.007) was observed in Plg deficient (Plg-/-) mice (VEGF - 0.36 mm, bFGF - 0.67 mm) compared to Plg+/+ mice (VEGF - 0.56 mm, bFGF - 0.85 mm).

Conclusions: These results demonstrate the importance of plasminogen, as well as of uPA, in angiogenesis in vivo.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cornea / metabolism
  • Extracellular Matrix / metabolism
  • Female
  • Fibroblast Growth Factor 2 / metabolism
  • Genotype
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neovascularization, Physiologic*
  • Plasminogen / metabolism
  • Plasminogen / physiology*
  • Receptors, Cell Surface / metabolism
  • Receptors, Urokinase Plasminogen Activator
  • Time Factors
  • Urokinase-Type Plasminogen Activator / metabolism

Substances

  • PLAUR protein, human
  • Plaur protein, mouse
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Fibroblast Growth Factor 2
  • Plasminogen
  • Urokinase-Type Plasminogen Activator