Regulation of plasminogen activator inhibitor 1 expression in human osteoarthritic chondrocytes by fluid shear stress: Role of protein kinase Cα

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.

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

European Journal of Inflammation ◽

10.1177/2058739218767292 ◽

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.

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Role of plasminogen activator inhibitor-1 in coronary pathophysiology

Thrombosis Research ◽

10.1016/j.thromres.2018.02.135 ◽

2018 ◽

Vol 164 ◽

pp. 54-62 ◽

Cited By ~ 16

Author(s):

Richard G. Jung ◽

Trevor Simard ◽

Alisha Labinaz ◽

F. Daniel Ramirez ◽

Pietro Di Santo ◽

...

Keyword(s):

Plasminogen Activator ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor

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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.bloodjournal711220 ◽

1988 ◽

Vol 71 (1) ◽

pp. 220-225 ◽

Cited By ~ 325

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.

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