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.

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.

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.

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.

Localization of Fibrinolytic Activators and Inhibitors in Normal and Atherosclerotic Vessels

1996 ◽  
Vol 75 (06) ◽  
pp. 933-938 ◽  
Author(s):  
Marten Fålkenberg ◽  
Johan Tjärnstrom ◽  
Per Örtenwall ◽  
Michael Olausson ◽  
Bo Risberg
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Vasa Vasorum ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Tissue Plasminogen ◽  
The Media ◽  
Activator Inhibitor ◽  
Pai 1

SummaryLocal fibrinolytic changes in atherosclerotic arteries have been suggested to influence plaque growth and promote mural thrombosis on ruptured or ulcerated plaques. Increased levels of plasminogen activator inhibitor (PAI-1) have been found in atherosclerotic arteries. In this study tissue plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and PAI-1 were localized in arterial biopsies of healthy and atherosclerotic vessels by immunohistochemis-try. The expression of fibrinolytic regulators was related to the distribution of endothelial cells (EC) and macrophages. Results: t-PA was expressed in vasa vasorum. PAI-1 was positive in endothelial cells, in the media and in the adventitia. Increased expression of t-PA, u-PA and PAI-1 was found in atherosclerotic vessels. t-PA, u-PA, PAI-1 and macrophages were co-localized in plaques. These results support the concept that macrophages can be important in the local regulation of fibrinolysis in atherosclerotic vessels.

Cellular Localisation in Placenta of Placental Type Plasminogen Activator Inhibitor

1986 ◽  
Vol 56 (01) ◽  
pp. 063-065 ◽  
Author(s):  
B Åstedt ◽  
I Hägerstrand ◽  
I Lecander
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Immunoreactive Material ◽  
Type Plasminogen Activator ◽  
Cellular Localisation ◽  
Immunohistochemical Methods ◽  
Activator Inhibitor ◽  
In Pregnancy

SummaryA specific plasminogen activator inhibitor is known to occur in placenta and in pregnancy plasma. Immunohistochemical methods with polyclonal and monoclonal antibodies against the inhibitor were used for its localisation in term placentas. Immunoreactive material was found in the trophoblastic epithelium. It was absent in the stroma of the chorion villi.

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