A Sensitive Assay, Specific for Endothelial Cell Type Plasminogen Activator Inhibitor in Blood Plasma

1986 ◽  
Vol 55 (01) ◽  
pp. 074-077 ◽  
Author(s):  
E D Sprengers
Keyword(s):  
Endothelial Cell ◽  
Blood Plasma ◽  
Plasminogen Activator ◽  
Inhibitory Activity ◽  
Plasminogen Activator Inhibitor ◽  
Cell Type ◽  
Inhibitory Component ◽  
Type Plasminogen Activator ◽  
Endothelial Cell Type ◽  
In Blood Plasma

SummaryA polyclonal antibody raised against plasminogen activator (PA-)inhibitor from endothelial cells fully precipitates the PA-inhibitor in endothelial cell conditioned medium but only a part of the PA-inhibitory activity in blood plasma. This indicates that the PA-inhibitory activity in blood plasma is not due to a single inhibitory component. Performing the assay for PA-inhibitory activity in plasma both in the presence and absence of saturating concentrations of anti-endothelial cell PA-inhibitor antibodies, allows the determination of endothelial cell type PA-inhibitor in plasma. The assay gives a linear dose-response curve of amount of plasma added versus t-PA neutralised.Values for endothelial cell type PA-inhibitor in plasma of a group of 20 healthy individuals are in the range of 0.0-16.8 IU/ml and are not normally distributed (median value 3.0 IU/ml).This method also reveals a second, so far unidentified, PA-inhibitory component in human plasma.

Blood Platelet Plasminogen Activator Inhibitor: Two Different Pools of Endothelial Cell Type Plasminogen Activator Inhibitor in Human Blood

1986 ◽  
Vol 55 (03) ◽  
pp. 325-329 ◽  
Author(s):  
E D Sprengers ◽  
J W N Akkerman ◽  
B G Jansen
Keyword(s):  
Endothelial Cell ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Blood Platelet ◽  
Healthy Population ◽  
Cell Type ◽  
High Turnover ◽  
Type Plasminogen Activator ◽  
Activator Inhibitor ◽  
Endothelial Cell Type

SummaryAn assay for plasminogen activator inhibitor in human platelets is described. With this assay we find an average value of 6.8 × 10−8 IU/platelet (S.D. = 3.0 × 10−8; n = 20) in a healthy population. We characterized the PA-inhibitor from platelets and identified it as endothelial cell type plasminogen activator inhibitor, by its immunologic and functional properties. Besides the plasma pool of plasminogen activator inhibitor with a very high turnover rate, platelets constitute a second pool of plasminogen activator inhibitor in the circulation of the same order of magnitude. The two different pools of plasminogen activator inhibitor might have a different physiologic function.

scholarly journals Thrombin neutralizes plasminogen activator inhibitor 1 (PAI-1) that is complexed with vitronectin in the endothelial cell matrix.

1991 ◽  
Vol 115 (6) ◽  
pp. 1773-1781 ◽  
Author(s):  
H J Ehrlich ◽  
R K Gebbink ◽  
K T Preissner ◽  
J Keijer ◽  
N L Esmon ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Cell Surface Receptor ◽  
Tissue Type ◽  
Plasminogen Activator Inhibitor 1 ◽  
Cell Matrix ◽  
Type Plasminogen Activator ◽  
Activator Inhibitor ◽  
Pai 1

Vitronectin endows plasminogen activator inhibitor 1 (PAI-1), the fast-acting inhibitor of both tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), with additional thrombin inhibitory properties. In view of the apparent association between PAI-1 and vitronectin in the endothelial cell matrix (ECM), we analyzed the interaction between PAI-1 and thrombin in this environment. Upon incubating 125I-labeled alpha-thrombin with endothelial cell matrix (ECM), the protease formed SDS-stable complexes exclusively with PAI-1, with subsequent release of these complexes into the supernatant. Vitronectin was required as a cofactor for the association between PAI-1 and thrombin in ECM. Metabolic labeling of endothelial cell proteins, followed by incubation of ECM with t-PA, u-PA, or thrombin, indicated that all three proteases depleted PAI-1 from ECM by complex formation and proteolytic cleavage. Proteolytically inactive thrombin as well as anticoagulant thrombin, i.e., thrombin in complex with its endothelial cell surface receptor thrombomodulin, did not neutralize PAI-1, emphasizing that the procoagulant moiety of thrombin is required for a functional interaction with PAI-1. A physiological implication of our findings may be related to the mutual neutralization of both PAI-1 and thrombin, providing a new link between plasminogen activation and the coagulation system. Evidence is provided that in ECM, procoagulant thrombin may promote plasminogen activator activity by inactivating PAI-1.

Deep Vein Thrombosis and Fibrinolysis

1991 ◽  
Vol 66 (04) ◽  
pp. 426-429 ◽  
Author(s):  
Marcel Levi ◽  
Anthonie W A Lensing ◽  
Harry R Büller ◽  
Paolo Prandoni ◽  
Gerard Dooijewaard ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Controlled Study ◽  
First Episode ◽  
Control Group ◽  
Vein Thrombosis ◽  
Type Plasminogen Activator ◽  
Deep Vein

SummaryIn the present study 57 consecutive patients with a first episode of venographically proven deep vein thrombosis were investigated to evaluate the release of tissue-type plasminogen activator (t-PA) and of urokinase-type plasminogen activator (u-PA) in response to DDAVP stimulation as well as the resting plasminogen activator inhibitor (PAI) concentration, comparing this to the results obtained in 66 similar patients with a clinical suspicion of thrombosis but with a normal venogram. All assays were performed without knowledge of the patient's status.Four patients in the deep vein thrombosis-group (7%) had an absent u-PA antigen response upon DDAVP infusion, while a normal response was observed in all control subjects. Patients and controls showed similar increases in t-PA antigen level upon DDAVP. High resting PAI antigen levels were encountered in 5 patients in the deep vein thrombosis-group (9%) and in 6 subjects in the control group (9%).The results from this controlled study indicate that a defective release of u-PA may occur in patients with deep vein thrombosis and may have pathogenetic significance. Furthermore it is concluded that elevation of PAI levels cannot be considered as a specific risk factor for venous thrombosis.

A Specific Immunologic Assay for Functional Plasminogen Activator Inhibitor 1 in Plasma – Standardized Measurements of the Inhibitor and Related Parameters in Patients with Venous Thromboembolic Disease

1992 ◽  
Vol 68 (05) ◽  
pp. 486-494 ◽  
Author(s):  
Malou Philips ◽  
Anne-Grethe Juul ◽  
Johan Selmer ◽  
Bent Lind ◽  
Sixtus Thorsen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Normal Subjects ◽  
Tissue Type ◽  
Blood Collection ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Significant Difference ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-l complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.

Effects of Moderate Alcohol Consumption on Platelet Function, Tissue-Type Plasminogen Activator and Plasminogen Activator Inhibitor

1990 ◽  
Vol 63 (03) ◽  
pp. 345-348 ◽  
Author(s):  
J Veenastra ◽  
C Kluft ◽  
Th Ockhuizen ◽  
H v d Pol ◽  
M Wedel ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Plasminogen Activator ◽  
Platelet Function ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Moderate Alcohol Consumption ◽  
Tissue Type Plasminogen Activator ◽  
Postprandial Phase ◽  
Type Plasminogen Activator ◽  
Activator Inhibitor

SummaryShort-term effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were studied in two age groups of volunteers (20–30 and 45–55 years), each consisting of eight healthy males. The alcohol (30 g in red port and wine) was consumed during a standard dinner. Two blood samples were drawn: one in the postprandial phase, and one the next morning after fasting overnight. Alcohol consumption tended to increase platelet aggregation and production of hydroxy fatty acids, reduced plasma t-PA activity and increased PAI activity in the postprandial phase. After the overnight fast the effects on t-PA and PAI had disappeared whereas at that time alcohol consumption tended to decrease platelet function. The effects of alcohol on t-PA and PAI activity appeared mainly in the older age group, whereas the t-PA activity in this group was already much lower, irrespective of alcohol consumption.

Fibrinolysis and Coagulation in Patients with Infectious Disease and Sepsis

1991 ◽  
Vol 65 (03) ◽  
pp. 291-295 ◽  
Author(s):  
J Philippé ◽  
F Offner ◽  
P J Declerck ◽  
G Leroux-Roels ◽  
D Vogelaers ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Plasminogen Activator ◽  
Protein C ◽  
Severe Infection ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Type Plasminogen Activator ◽  
Significant Difference ◽  
At Iii ◽  
C 30

SummarySepsis is often associated with hemostatic dysfunction. This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome. Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease. The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 ± 9.4 versus 1.6 ± 1.5 ng/ml, p <0.0001). PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 ± 390 ng/ml versus 120 ± 200 ng/ml, and 3.0 ± 3.6 IU/ml versus 1.0 ± 0.7 IU/ml, respectively, p <0.01). AT III was decreased in sepsis patients (58 ± 28% in sepsis versus 79 ± 26% in severe infectious disease, p <0.01) as was protein C (30 ± 18% versus 58 ± 27%, p <0.001). No significant difference was found for t-PA antigen nor for PAI activity. Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity. It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection. u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease.

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