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

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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Detection of plasminogen activator inhibitor-1 (-675 4G/5G) gene polymorphism in women with recurrent abortion

Hematology & Transfusion International Journal ◽

10.15406/htij.2018.07.00203 ◽

2019 ◽

Vol 7 (2) ◽

pp. 41-44

Author(s):

Iglal Youssef Shaala ◽

Akram Abdel Moneim Deghady ◽

Reham Abdel Haleem Abo Elwafa ◽

Tamer Ahmed Hosny ◽

Engy Taher Ammar

Keyword(s):

Gene Polymorphism ◽

Plasminogen Activator ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Plasminogen Activator Inhibitor ◽

Recurrent Abortion ◽

Plasminogen Activator Inhibitor 1 ◽

Uterine Anomalies ◽

Activator Inhibitor ◽

Pai 1

Background: recurrent abortion is considered one of the most common complications that occur during pregnancy and counts for 15% of pregnancies that are recognized clinically. Many causes can be attributed to the recurrent pregnancy loss e.g. chromosomal anomalies, thrombophilic disorders, uterine anomalies, endocrine abnormalities and fetal anomalies. Thrombophilia can be either hereditary or acquired. Multiple genes had been implicated in the pathogenesis of the thrombophilia. Previous studies have indicated that genetic polymorphism of the plasminogen activator inhibitor-1 gene (PAI-1) may be associated with recurrent abortion. Aim: The aim of the present study was to investigate whether plasminogen activator inhibitor-1 (-675 4G/5G) gene polymorphism is associated with the occurrence of recurrent pregnancy loss or not. Methods: DNA samples were collected from sixty six female patients with recurrent abortion (33 primary abortion, 33 secondary abortion) and thirty four healthy controls with normal pregnancy for detection of plasminogen activator inhibitor-1 (-675 4G/5G) gene polymorphism by restriction fragment length polymorphism PCR. Results: there was a significant association between PAI-1(-675 4G/5G) polymorphism and the occurrence of recurrent pregnancy loss. Conclusion: Our results assumed that PAI-1 (-675 4G/5G) polymorphism is associated with recurrent pregnancy loss.

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The Relationship Between Plasminogen Activator Inhibitor-1 (PAI-1) A15T Gene Polymorphism And Prognosis Of Pulmonary Adenocarcinoma In Korean Population

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a5148 ◽

2011 ◽

Author(s):

Ju Eun Lim ◽

Young Ae Kang ◽

Moo Suk Park

Keyword(s):

Gene Polymorphism ◽

Plasminogen Activator ◽

Plasminogen Activator Inhibitor ◽

Pulmonary Adenocarcinoma ◽

Korean Population ◽

Plasminogen Activator Inhibitor 1 ◽

The Relationship ◽

Activator Inhibitor ◽

Pai 1

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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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W1490: Association Between Plasma Levels of Plasminogen Activator Inhibitor-1 (PAI-1) and Colorectal Adenomas

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2010.03.902 ◽

2010 ◽

Vol 71 (5) ◽

pp. AB341

Author(s):

Eun Ran Kim ◽

Moon Hee Yang ◽

Yeun Jung Lim ◽

Jin Hee Lee ◽

Byung-Hoon Min ◽

...

Keyword(s):

Plasminogen Activator ◽

Plasma Levels ◽

Plasminogen Activator Inhibitor ◽

Colorectal Adenomas ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

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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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Impact of statin therapy on plasma levels of plasminogen activator inhibitor-1

Thrombosis and Haemostasis ◽

10.1160/th15-10-0770 ◽

2016 ◽

Vol 116 (07) ◽

pp. 162-171 ◽

Cited By ~ 14

Author(s):

Amirhossein Sahebkar ◽

Cristiana Catena ◽

Kausik Ray ◽

Antonio Vallejo-Vaz ◽

Željko Reiner ◽

...

Keyword(s):

Statin Therapy ◽

Plasminogen Activator ◽

Publication Bias ◽

Plasma Levels ◽

Meta Analysis ◽

Plasminogen Activator Inhibitor ◽

Lipid Lowering ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

SummaryElevated plasma levels of the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 (PAI-1) may contribute to the pathogenesis of atherosclerotic cardiovascular disease. Beyond their lipid-lowering effect, statins have been shown to modulate plasma PAI-1 levels but evidence from individual randomised controlled trials (RCTs) is controversial. Therefore, we aimed to assess the potential effects of statin therapy on plasma PAI-1 concentration through a meta-analysis of RCTs. We searched Medline and SCOPUS databases (up to October 3, 2014) to identify RCTs investigating the effect of statin therapy on plasma PAI-1 concentrations. We performed random-effects meta-analysis and assessed heterogeneity (I2 test, subgroup and sensitivity analyses) and publication bias (funnel plot, Egger and “trim and fill” tests). Sixteen RCTs (comprising 19 treatment arms) were included and pooled analyses showed a significant effect of statins in reducing plasma PAI-1 concentrations (weighted mean difference WMD: –15.72 ng/ml, 95 % confidence interval [CI]: –25.01, –6.43,). In subgroup analysis, this effect remained significant in with lipophilic statins (atorvastatin and simvastatin) (WMD: –21.32 ng/ml, 95 % CI: –32.73, –9.91, I2=99 %) and particularly atorvastatin (WMD: –20.88 ng/mL, 95 % CI: –28.79, –12.97, I2=97 %). In the meta-regression analysis, the impact of statins on PAI-1 did not correlate with the administered dose, duration of treatment and changes in plasma LDL-cholesterol concentrations. Finally, evidence of publication bias was observed. In conclusion, taking into account the limit of heterogeneity between studies, the present meta-analysis suggests that statin therapy (mainly atorvastatin) significantly lowers plasma PAI-1 concentrations.

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