The role of plasminogen in angiogenesis in vivo

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 Pig deficient (Pig -/-/) 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. © 2003 International Society on Thrombosis and Haemostasis.