The role of plasminogen in angiogenesis in vivo.
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.
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Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, OH 44195, USA.
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D000818:Animals; D003315:Cornea / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D010958:Plasminogen / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D016222:Fibroblast Growth Factor 2; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator