Role of fibrinolytic parameters and plasminogen activator inhibitor 1 (PAI-1) promoter polymorphism on premature atherosclerosis in SLE patients

An enzyme-linked immunosorbent assay for plasminogen activator inhibitor-1 (PAI-1) in biologic fluids was developed on the basis of two murine monoclonal antibodies raised against PAI-1 purified from HT- 1080 fibrosarcoma cells. The lower limit of sensitivity of the assay in plasma is 2 ng/mL. The assay is 12 times less sensitive toward the PAI- 1/human tissue-type plasminogen activator (t-PA) complex as compared with free PAI-1. The intraassay, interassay, and interdilution coefficients of variation are 5.2%, 8.0%, and 7.1%, respectively. The level of PAI-1 in platelet-poor plasma of healthy subjects is 18 +/- 10 ng/mL (mean +/- SD, n = 45). In platelet-rich plasma after freezing and thawing, 92% of PAI-1 antigen is released from platelets, whereas only 8% is found in the corresponding platelet-poor plasma. In platelet-poor plasma from healthy subjects, a linear correlation (r = 0.80) was found between PAI activity and PAI-1 antigen. In plasma approximately two thirds of the PAI-1 antigen was functionally active, whereas only 5% of the PAI-1 antigen released from platelets was active. During pregnancy a progressive increase of PAI-1 antigen levels up to three- to sixfold the control value was observed. In plasma of patients with recurrent deep vein thrombosis, PAI-1 levels were 44 +/- 20 ng/mL (mean +/- SD, n = 7), during a clinically silent phase. Four of these patients had a level above 38 ng/mL (mean +/- 2 SD of normal). The present assay, based on stable and reproducible reagents, allows the specific determination of PAI-1 antigen in biologic fluids. It may facilitate interlaboratory comparisons and be useful for further investigations of the role of PAI-1 in clinical conditions associated with impaired fibrinolysis and/or a tendency to thrombosis and investigations of the role of PAI-1 in platelets.

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Measurement of plasminogen activator inhibitor 1 in biologic fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay

Blood ◽

10.1182/blood.v71.1.220.220 ◽

1988 ◽

Vol 71 (1) ◽

pp. 220-225 ◽

Cited By ~ 72

Author(s):

PJ Declerck ◽

MC Alessi ◽

M Verstreken ◽

EK Kruithof ◽

I Juhan-Vague ◽

...

Keyword(s):

Plasminogen Activator ◽

Immunosorbent Assay ◽

Healthy Subjects ◽

Plasminogen Activator Inhibitor ◽

Enzyme Linked Immunosorbent Assay ◽

Plasminogen Activator Inhibitor 1 ◽

Platelet Poor Plasma ◽

Activator Inhibitor ◽

Pai 1

Abstract An enzyme-linked immunosorbent assay for plasminogen activator inhibitor-1 (PAI-1) in biologic fluids was developed on the basis of two murine monoclonal antibodies raised against PAI-1 purified from HT- 1080 fibrosarcoma cells. The lower limit of sensitivity of the assay in plasma is 2 ng/mL. The assay is 12 times less sensitive toward the PAI- 1/human tissue-type plasminogen activator (t-PA) complex as compared with free PAI-1. The intraassay, interassay, and interdilution coefficients of variation are 5.2%, 8.0%, and 7.1%, respectively. The level of PAI-1 in platelet-poor plasma of healthy subjects is 18 +/- 10 ng/mL (mean +/- SD, n = 45). In platelet-rich plasma after freezing and thawing, 92% of PAI-1 antigen is released from platelets, whereas only 8% is found in the corresponding platelet-poor plasma. In platelet-poor plasma from healthy subjects, a linear correlation (r = 0.80) was found between PAI activity and PAI-1 antigen. In plasma approximately two thirds of the PAI-1 antigen was functionally active, whereas only 5% of the PAI-1 antigen released from platelets was active. During pregnancy a progressive increase of PAI-1 antigen levels up to three- to sixfold the control value was observed. In plasma of patients with recurrent deep vein thrombosis, PAI-1 levels were 44 +/- 20 ng/mL (mean +/- SD, n = 7), during a clinically silent phase. Four of these patients had a level above 38 ng/mL (mean +/- 2 SD of normal). The present assay, based on stable and reproducible reagents, allows the specific determination of PAI-1 antigen in biologic fluids. It may facilitate interlaboratory comparisons and be useful for further investigations of the role of PAI-1 in clinical conditions associated with impaired fibrinolysis and/or a tendency to thrombosis and investigations of the role of PAI-1 in platelets.

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Plasminogen activator inhibitor-1 and tumour growth, invasion, and metastasis

Thrombosis and Haemostasis ◽

10.1160/th03-12-0784 ◽

2004 ◽

Vol 91 (03) ◽

pp. 438-449 ◽

Cited By ~ 98

Author(s):

Michelle Durand ◽

Julie Bødker ◽

Anni Christensen ◽

Daniel Dupont ◽

Martin Hansen ◽

...

Keyword(s):

Plasminogen Activator ◽

Molecular Interactions ◽

Plasminogen Activator Inhibitor ◽

Biological Functions ◽

Invasion And Metastasis ◽

Plasminogen Activator Inhibitor 1 ◽

Human Tumours ◽

Activator Inhibitor ◽

Pai 1

SummaryIn recent decades, evidence has been accumulating showing the important role of urokinase-type plasminogen activator (uPA) in growth, invasion, and metastasis of malignant tumours. The evidence comes from results with animal tumour models and from the observation that a high level of uPA in human tumours is associated with a poor patient prognosis. It therefore initially came as a surprise that a high tumour level of the uPA inhibitor plasminogen activator inhibitor-1 (PAI-1) is also associated with a poor prognosis, the PAI-1 level in fact being one of the most informative biochemical prognostic markers. We review here recent investigations into the possible tumour biological role of PAI-1, performed by animal tumour models, histological examination of human tumours, and new knowledge about the molecular interactions of PAI-1 possibly underlying its tumour biological functions. The exact tumour biological functions of PAI-1 remain uncertain but PAI-1 seems to be multifunctional as PAI-1 is expressed by multiple cell types and has multiple molecular interactions. The potential utilisation of PAI-1 as a target for anti-cancer therapy depends on further mapping of these functions.

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Role of functional plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism in susceptibility, severity, and outcome of meningococcal disease in Caucasian children*

Critical Care Medicine ◽

10.1097/01.ccm.0000100122.57249.5d ◽

2003 ◽

Vol 31 (12) ◽

pp. 2788-2793 ◽

Cited By ~ 76

Author(s):

Elene Haralambous ◽

Martin L. Hibberd ◽

Peter W. M. Hermans ◽

Nelly Ninis ◽

Simon Nadel ◽

...

Keyword(s):

Plasminogen Activator ◽

Meningococcal Disease ◽

Plasminogen Activator Inhibitor ◽

Promoter Polymorphism ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor

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Role of 4G/5G plasminogen activator inhibitor-1 (PAI-1) gene polymorphism and the PAI-1 plasma levels in the outcome of patients with severe sepsis

Critical Care ◽

10.1186/cc7516 ◽

2009 ◽

Vol 13 (Suppl 1) ◽

pp. P352 ◽

Cited By ~ 2

Author(s):

L Lorente ◽

M Martín ◽

L Labarta ◽

C Díaz ◽

J Solé-Violán ◽

...

Keyword(s):

Severe Sepsis ◽

Gene Polymorphism ◽

Plasminogen Activator ◽

Plasma Levels ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

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Plasminogen activator inhibitor-1 (PAI-1) activity post myocardial infarction: the role of acute phase reactants, insulin-like molecules and promoter (4G/5G) polymorphism in the PAI-1 gene

Atherosclerosis ◽

10.1016/s0021-9150(03)00095-9 ◽

2003 ◽

Vol 168 (2) ◽

pp. 297-304 ◽

Cited By ~ 9

Author(s):

A Panahloo

Keyword(s):

Myocardial Infarction ◽

Plasminogen Activator ◽

Acute Phase ◽

Plasminogen Activator Inhibitor ◽

Post Myocardial Infarction ◽

Plasminogen Activator Inhibitor 1 ◽

Acute Phase Reactants ◽

Activator Inhibitor ◽

Pai 1

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Role of plasminogen activator inhibitor-1 in promoting fibrin deposition in rabbits infused with ancrod or thrombin

Blood ◽

10.1182/blood.v82.12.3631.bloodjournal82123631 ◽

1993 ◽

Vol 82 (12) ◽

pp. 3631-3636 ◽

Cited By ~ 1

Author(s):

C Krishnamurti ◽

C Bolan ◽

CA Colleton ◽

TM Reilly ◽

BM Alving

Keyword(s):

Plasminogen Activator ◽

Plasminogen Activator Inhibitor ◽

Fibrin Deposition ◽

Plasminogen Activator Inhibitor 1 ◽

Elevated Activity ◽

Activator Inhibitor ◽

Pai 1

The role of defective fibrinolysis caused by elevated activity of plasminogen activator inhibitor-1 (PAI-1) in promoting fibrin deposition in vivo has not been well established. The present study compared the efficacy of thrombin or ancrod, a venom-derived enzyme that clots fibrinogen, to induce fibrin formation in rabbits with elevated PAI-1 levels. One set of male New Zealand rabbits received intravenous endotoxin to increase endogenous PAI-1 activity followed by a 1-hour infusion of ancrod or thrombin; another set of normal rabbits received intravenous human recombinant PAI-1 (rPAI-1) during an infusion of ancrod or thrombin. Thirty minutes after the end of the infusion, renal fibrin deposition was assessed by histopathology. Animals receiving endotoxin, rPAI-1, ancrod, or thrombin alone did not develop renal thrombi. All endotoxin-treated rabbits developed fibrin deposition when infused with ancrod (n = 4) or thrombin (n = 6). Fibrin deposition occurred in 7 of 7 rabbits receiving both rPAI-1 and ancrod and in only 1 of 6 receiving rPAI-1 and thrombin (P “ .01). In vitro, thrombin but not ancrod was inactivated by normal rabbit plasma and by purified antithrombin III or thrombomodulin. The data indicate that elevated levels of PAI-1 promote fibrin deposition in rabbits infused with ancrod but not with thrombin. In endotoxin-treated rabbits, fibrin deposition that occurs with thrombin infusion may be caused by decreased inhibition of procoagulant activity and not increased PAI-1 activity.

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