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Endothelium-fibrinolysis system interaction.

K Sueishi, C Yasunaga, Y Nakashima

Nihon Ketsueki Gakkai Zasshi : Journal of Japan Haematological Society

|December 1, 1989

Summary

Urokinase-type plasminogen activator (u-PA) from bovine endothelial cells (BCE) promotes capillary growth. Plasminogen significantly enhances tube formation, crucial for understanding angiogenesis in disease.

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Area of Science:

Cell Biology
Biochemistry
Physiology

Background:

Angiogenesis, the formation of new blood vessels, is a complex process.
Urokinase-type plasminogen activator (u-PA) is a key enzyme in the fibrinolytic system.
The role of u-PA in endothelial cell capillary growth requires further elucidation.

Purpose of the Study:

To investigate the role of urokinase-type plasminogen activator (u-PA) in capillary growth using cultured bovine endothelial cells (BCE).
To quantitatively assess angiogenesis in vitro and evaluate the effects of fibrinolytic proteases and other reagents.

Main Methods:

Cultured bovine endothelial cells (BCE) were grown on type I collagen gels.
Morphometrical analyses were performed to measure tube formation and quantitatively assess angiogenesis.
The effects of plasminogen, basic fibroblast growth factor, anti-u-PA IgG, anti-plasmin reagents, transforming growth factor beta, tumor necrosis factor alpha, and interleukin-1 were evaluated.

Main Results:

BCE formed capillary-like networks in collagen gels.
Plasminogen significantly increased BCE tube formation in a dose-dependent manner.
Basic fibroblast growth factor enhanced tube formation only with plasminogen.
Inhibitors of u-PA and plasmin suppressed these enhancing effects, indicating u-PA's role.
Transforming growth factor beta enhanced tube formation, while tumor necrosis factor alpha and interleukin-1 suppressed it.

Conclusions:

Bovine endothelial cell-derived urokinase-type plasminogen activator (u-PA) plays a significant role in promoting capillary growth.
Plasminogen availability is crucial for u-PA-mediated angiogenesis.
This quantitative in vitro assay is valuable for studying neovascularization mechanisms in pathological conditions.

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