scholarly journals Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia

2009 ◽  
Vol 26 (3) ◽  
pp. 127-133 ◽  
Author(s):  
Menha Swellam ◽  
Nervana Samy ◽  
Susan Abdl Wahab ◽  
Mohamed Saeed Ibrahim
Keyword(s):  
Inflammatory Markers ◽  
Linear Regression Analysis ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
New Approach ◽  
Reactive Protein ◽  
Diagnostic Role ◽  
Activator Inhibitor ◽  
Pai 1

Objectives:Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE). Authors determine the clinical diagnostic role for thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1) as endothelial markers and C-reactive protein (CRP), and interlukin-6 (IL-6) as inflammatory markers when tested independently or in combinations.Materials and methods:We conducted a retrospective study in a cohort of 185 women grouped as 80 women with PE, 55 normotensive pregnant and 50 healthy non-pregnant. Plasma levels of TM, PAI-1, CRP and IL-6 were examined using enzyme linked immunosorbent assays.Results:Median levels and the positivity rates for the investigated markers were higher in PE as compared to the other groups (P< 0.0001). Using linear regression analysis, the investigated markers were significantly correlated regarding healthy nonpregnantvsPE or normotensive pregnantvsPE. The sensitivity of PAI-1 was the highest (98%) among the tested biomarkers. Combination between the investigated markers revealed absolute sensitivity (100%) and reliable specificity especially when PAI-1 was combined with CRP at 83% specificity.Conclusions:Investigated endothelial and inflammatory markers revealed sensitive diagnostic test for PE. However, coupled combination between PAI-1 with CRP showed superior both sensitivity and specificity which represent a promising new approach for detection of PE.

scholarly journals Role of plasminogen activator inhibitor-1 gene polymorphisms in osteoporosis: A study in Chinese post-menopausal women

2018 ◽  
Vol 16 ◽  
pp. 205873921876729
Author(s):  
An Wan ◽  
Daodong Liu
Keyword(s):  
Gene Polymorphisms ◽  
Chinese Women ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Post Menopausal ◽  
Activator Inhibitor ◽  
Pai 1

Osteoporosis is a chronic multifactorial disease characterized by deterioration of bone mass and is vulnerable to bone fracture. Plasminogen activator inhibitor-1 (PAI-1) is an important molecule for maintenance of optimum bone mass. Several single-nucleotide polymorphisms (SNPs) in PAI-1 have been reported to alter PAI-1 expression and/or the translational level. In this report, we explored the possible role of common PAI-1 gene polymorphisms on predisposition to osteoporosis in a Chinese cohort. A total of 364 post-menopausal Chinese women diagnosed of having osteoporosis and 350 healthy females hailing from similar areas were enrolled in this study. Five common SNPs (−844G > A, −6754G/5G, +43G > A, +9785G > A and +11053T > G) were genotyped by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). Relative expression of PAI-1 mRNA and plasma PAI-1 levels were quantified by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Prevalence of homozygous mutant (5G/5G) and minor allele (5G) of PAI-1 (−675 4G/5G) polymorphism was significantly more frequent in patients than in healthy controls (5G/5G: P < 0.0001, odds ratio (OR) = 3.18; 5G: P < 0.0001, OR = 1.65). Both plasma PAI-1 and relative mRNA expression levels were significantly lower in patients compared to healthy controls. Interestingly, the quantity of plasma PAI-1 and mRNA expression was correlated with PAI-1 (−675 4G/5G) polymorphism: subjects with 4G/4G genotype had elevated PAI-1 in comparison to homozygous mutant, and displayed lower quantity of PAI-1 protein and mRNA values. PAI-1 (−675 4G/5G) mutant is associated with susceptibility to development of osteoporosis in post-menopausal Chinese women. Furthermore, this variant in the promoter region alters plasma protein levels and relative expression of PAI-1.

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

Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 220-225 ◽  
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

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.

Abstract 43: Association of Plasminogen Activator Inhibitor-1 with Prevalent and Incident Obesity is Independent of Inflammatory Markers: The Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Sadiya S Khan ◽  
Donald M Lloyd-Jones ◽  
Cheelin Chan ◽  
Kiang Liu ◽  
Mary Cushman ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Inflammatory Markers ◽  
Smoking Status ◽  
Plasminogen Activator Inhibitor ◽  
Cox Proportional Hazards ◽  
Plasminogen Activator Inhibitor 1 ◽  
Ethnic Study ◽  
Activator Inhibitor ◽  
Pai 1

Background: In experimental animal models, deficiency of plasminogen activator inhibitor-1 (PAI-1) protects against development of obesity. In addition, elevated circulating levels of PAI-1 are associated in cross-sectional studies with prevalent obesity in humans. However, no studies have investigated the prospective association between PAI-1 and incident obesity. Methods: Plasma PAI-1 levels were measured in a random sample of men and women at baseline (2000-2002) in the Multi-Ethnic Study of Atherosclerosis. Obesity was defined as body mass index (BMI) > 30kg/m2. Incident obesity was identified at four follow-up exams (2002-2011) among those who were not obese at baseline. Logistic regression was used to examine the odds ratios (OR) and 95% confidence intervals (CI) of prevalent obesity at baseline. Cox proportional hazards regression was used to estimate hazard ratios (HR) for time to incident obesity. The covariates used for adjustment included baseline demographics (age, race, sex, center), lifestyle risk factors (physical activity, dietary energy intake, smoking status, alcohol consumption, education), and inflammatory markers (CRP and IL-6). Results: In 839 participants mean age was 59 years old; 59% and 47% of the cohort were female and white, respectively. At baseline, each standard deviation (SD) increase in log(PAI-1) level was associated with an odds ratio (OR) for adjusted prevalent obesity of 2.70 (95% CI: 2.21 - 3.30, p<0.001. This association remained significant after further adjustment for IL-6 and CRP with OR 2.39 (95% CI: 1.94-2.94, p<0.001). Over a median follow-up of 8.5 years, 16% of participants developed obesity. The multivariable adjusted hazard ratio for incident obesity was 1.36 (95% CI 1.09-1.69, p<0.001) per 1 SD increase in log(PAI-1). (Table). Conclusions: Elevated PAI-1 levels are associated with prevalent and incident obesity. These findings are consistent with results from murine studies and provide evidence suggesting a potential role of PAI-1 in the pathogenesis of obesity.

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

Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 220-225 ◽  
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.

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

2004 ◽  
Vol 91 (03) ◽  
pp. 438-449 ◽  
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.

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

Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3631-3636 ◽  
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.

The Role of the Finger Domain of Tissue-type Plasminogen Activator (t-PA) and Plasminogen Activator Inhibitor 1 (PAI-1) in Initiation and Progression of Thrombolysis

1994 ◽  
Vol 72 (06) ◽  
pp. 900-905 ◽  
Author(s):  
Harold A R Stringer ◽  
Peter van Swieten ◽  
Anton J G Horrevoets ◽  
Annelies Smilde ◽  
Hans Pannekoek
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Activator Inhibitor ◽  
Pai 1

SummaryWe further investigated the role of the finger (F) and the kringle-2 (K2) domains of tissue-type plasminogen activator (t-PA) in fibrin-stimulated plasminogen activation. To that end, the action of purified (wt) t-PA or of variants lacking F (del.F) or K2 (del.K2) was assessed either in a static, human whole blood clot-lysis system or in whole blood thrombi generated in the “Chandler loop”. In both clot-lysis systems, significant differences were observed for the initiation of thrombolysis with equimolar concentrations of the t-PA variants. A relatively minor “lag phase” occurred in thrombolysis mediated by wt t-PA, whereas a 6.4-fold and 1.6-fold extension is found for del.F and del.K2, respectively. We observed identical lag-times, characteristic for each t-PA variant, in platelet-rich heads and in platelet-poor tails of thrombi. Since plasminogen activator inhibitor 1 (PAI-1) is preferentially retained in the platelet-rich heads, we conclude that the inhibitor does not interfere with the initial stage of thrombolysis but exerts its action in later stages, resulting in a reduction of the rate of clot lysis. A complementation clot-lysis assay was devised to study a potential interplay of del.F and del.K2. Accordingly, clot lysis was determined with combinations of del.F and del.K2 that were inversely varied in relation to equipotent dosage to distinguish between additive, antagonistic or synergistic effects of these variants. The isobole for combinations of del.F and del.K2 shows an independent, additive action of del.F and del.K2 in clot lysis. Under the conditions employed, namely a relatively high concentration of fibrin and Glu-plasminogen and a low concentration of t-PA variant, our data show: i) the crucial role of the F domain and the lack of effect of PAI-1 in initiation of thrombolysis, ii) the lack of importance of the fibrimbinding domains of t-PA and the regulatory role of PAI-1 in advanced stages of thrombolysis.

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