Direct interactions of plasminogen activators with human aortic and pulmonary artery endothelial cells in vitro: implications for thrombolytic therapy.

Abstract

Direct interactions of plasminogen activators with arterial endothelial cells are important in the pathogenesis of vascular complications associated with thrombolytic therapy. We investigated the direct effects of various plasminogen activators on human aortic and pulmonary artery endothelial cell functions in vitro. The effects of plasminogen activators on endothelial cells were not caused by generation of plasmin, as shown by the absence of plasminogen and alpha(2)-plasmin inhibitor-plasmin complex both before and after addition of plasminogen activators to endothelial cells. High concentrations of plasminogen activators increased the permeability of aortic endothelial cells to albumin. Alteplase (50 x 10(3) IU/ml), a recombinant tissue-type plasminogen activator (t-PA), increased prostaglandin I(2) (PGI(2)) production by aortic endothelial cells from 175.5 +/- 13.8 to 870.8 +/- 131.0 pg/mg cellular protein during a 2-h incubation; other plasminogen activators increased PGI(2) production to a lesser extent. Alteplase (100 x 10(3) IU/ml) also increased PGI(2) production from 152.0 +/- 16.2 to 1,080 +/- 95.1 pg/mg cellular protein in human pulmonary artery endothelial cells. High concentrations of urokinases decreased the amount of endothelin-1 in the medium of aortic or pulmonary artery endothelial cells by as much as 93%; part of this decrease was attributable to degradation of endothelin-l by urokinases. Other plasminogen activators either had no effect on or slightly increased the production of endothelin-1. These changes in the function of human arterial endothelial cells induced by plasminogen activators may affect regional vascular tone, endothelial permeability, and platelet aggregability, all of which are important in the efficacy of thrombolysis and in the pathogenesis of such vascular complications as rethrombosis and hemorrhage.

• Authors: Y Yamada, M Yokota
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 27 Issue 5 Pg. 629-35 (May 1996) ISSN: 0160-2446 [Print] United States
• PMID: 8859931 (Publication Type: Journal Article)

Chemical References

• Endothelin-1
• Epoprostenol
• Plasminogen Activators

Topics

• Aorta (drug effects)
• Cells, Cultured
• Endothelin-1 (biosynthesis)
• Endothelium, Vascular (cytology, drug effects)
• Epoprostenol (biosynthesis)
• Humans
• Plasminogen Activators (pharmacology)
• Pulmonary Artery (drug effects)
• Thrombolytic Therapy