Plasmin-mediated proteolysis of vascular endothelial cell heparin releasable tissue factor pathway inhibitor.

Abstract

BACKGROUND:

Fibrinolytic therapy represents a widely available and effective treatment modality for ST segment elevation myocardial infarction (MI). Its overall benefit is attenuated by a high incidence of coronary arterial reocclusion.

METHODS/RESULTS:

Human umbilical vein endothelial cells (HUVEC) were incubated with unfractionated heparin (1.5 U/ml) (to provoke tissue factor pathway inhibitor [TFPI] release) followed by the addition of varying concentrations of alteplase (recombinant tissue plasminogen activator), plasminogen, their combination or plasmin alone. In the presence of 20% TFPI-depleted human plasma, there was a concentration-dependent decrease in TFPI levels following incubation with alteplase (28% reduction at 200 ng/ml; P < 0.01); 37% reduction at 1000 ng/ml (P < 0.001). Similar effects were observed for alteplase combined with plasminogen (P < 0.001), plasmin alone (P < 0.001) and with HUVEC incubated with low concentrations of plasmin (10 ng/ml) prior to heparin exposure.

CONCLUSIONS:

Plasmin, a non-specific protease, degrades vascular endothelial cell (constitutive) TFPI and heparin-releasable TFPI, attenuating an important pathway of vascular surface thromboresistance and potentially contributing to coronary arterial reocclusion after fibrinolytic therapy.

• Authors: You fu Li, Frederick A Spencer, Richard C Becker
• Journal: Journal of thrombosis and thrombolysis (J Thromb Thrombolysis) Vol. 15 Issue 1 Pg. 19-23 (Feb 2003) ISSN: 0929-5305 [Print] Netherlands
• PMID: 14574072 (Publication Type: Journal Article)

Chemical References

• Fibrinolytic Agents
• Lipoproteins
• lipoprotein-associated coagulation inhibitor
• Heparin
• Peptide Hydrolases
• Tissue Plasminogen Activator
• Fibrinolysin

Topics

• Coronary Artery Disease (chemically induced)
• Dose-Response Relationship, Drug
• Endothelium, Vascular (cytology, metabolism, physiology)
• Fibrinolysin (physiology)
• Fibrinolytic Agents (pharmacology)
• Heparin (pharmacology)
• Humans
• Lipoproteins (drug effects, metabolism)
• Peptide Hydrolases (metabolism)
• Recurrence
• Tissue Plasminogen Activator (pharmacology)
• Umbilical Veins