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PAI-1 Levels (pai-1 + level)

Distribution by Scientific Domains

Medical Sciences	100%

Kinds of PAI-1 Levels

plasma pai-1 level

Selected Abstracts

Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010
Paola Giordano
In a group of newly diagnosed acute lymphocytic leukemia (ALL) children we evaluated a number of hemostatic and inflammatory markers at diagnosis and at different time points during chemotherapy for the remission induction to identify alterations in the plasma levels of prothrombotic markers before and during the course of chemotherapy. The following plasma markers were evaluated: thrombin-antithrombin complex (TAT), D-Dimer, plasminogen activator inhibitor 1 (PAI-1), antithrombin, fibrinogen, von Willebrand factor (VWF) antigen and high molecular weight VWF (HMW-VWF) multimers, P-selectin, tumor necrosis factor alpha (TNF-,), and interleukin 6 (IL-6). Plasma samples were collected at the following time points: at T0 (baseline) and T1 (+24 days of therapy), T2 (+36 days therapy), and T3 (+64 days therapy). The results show that, at diagnosis, ALL children presented with laboratory signs of increased thrombin generation and fibrin formation (i.e. high TAT and D-dimer levels), fibrinolysis inhibition (i.e. high PAI-1 level), endothelial activation (i.e., high HMW-VWF and soluble P-selectin levels) and inflammation (i.e. high TNF-alpha and IL-6 levels). After starting induction therapy, the thrombin generation markers and inflammatory cytokines significantly decreased. To the opposite, PAI-1 and P-selectin significantly increased, suggesting an insult by chemotherapy on the vascular endothelium. These effects were more evident during steroid administration. Symptomatic venous thromboembolism (VTE) episodes developed in two cases during induction therapy, which did not allow the evaluation of the predictive value for VTE of laboratory markers. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source]

A-G-4G haplotype of PAI-1 gene polymorphisms ,844 G/A, HindIII G/C, and ,675 4G/5G is associated with increased risk of ischemic stroke caused by small vessel disease

ACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009
M. G. Adamski
Background,,, Plasminogen activator inhibitor type 1 (PAI-1) is the major inhibitor of fibrinolysis. It was reported that PAI-1 gene polymorphisms affected PAI-1 level and might therefore influence the risk of vascular diseases, including stroke. We studied the association of three common polymorphisms in PAI-1 gene (,844 G/A, ,675 4G/5G, and HindIII G/C) with the odds of different causes of ischemic stroke. Methods,,, We studied 390 patients with ischemic stroke due to large vessel disease (n = 117), small vessel disease (n = 121), and cardioembolism (n = 152) as well as 291 controls. The etiology of ischemic stroke was established using TOAST criteria. PAI-1 polymorphisms were genotyped with restriction fragment length polymorphism and single strand conformation polymorphism method. Results,,, A-G-4G haplotype of PAI-1 gene was found more frequently in stroke patients with small vessel disease than in control subjects (44.9% vs 35.7%; P = 0.02). No association was found between investigated genotype or allele frequencies and distinct causes of ischemic stroke. Conclusions,,, Our results demonstrate that A-G-4G PAI-1 gene haplotype is associated with increased risk of small vessel disease stroke, but this study does not support an association of ,844 G/A, ,675 4G/5G, and HindIII G/C PAI-1 gene polymorphisms with particular etiology of ischemic stroke. [source]

Plasminogen activator inhibitor-1 and asthma: role in the pathogenesis and molecular regulation

CLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2009
Z. Ma
Summary Plasminogen activator inhibitor (PAI)-1 is a major inhibitor of the fibrinolytic system. PAI-1 levels are markedly increased in asthmatic airways, and mast cells (MCs), a pivotal cell type in the pathogenesis of asthma, are one of the main sources of PAI-1 production. Recent studies suggest that PAI-1 may promote the development of asthma by regulating airway remodelling, airway hyperresponsiveness (AHR), and allergic inflammation. The single guanosine nucleotide deletion/insertion polymorphism (4G/5G) at ,675 bp of the PAI-1 gene is the major genetic determinant of PAI-1 expression. Plasma PAI-1 level is higher in people with the 4G/4G genotype than in those with the 5G/5G genotype. A strong association between the 4G/5G polymorphism and the risk and the severity of asthma has been suggested. Levels of plasma IgE and PAI-1 and severity of AHR are greater in asthmatic patients with the 4G/4G genotype than in those with the 5G/5G genotype. The PAI-1 promoter with the 4G allele renders higher transcription activity than the PAI-1 promoter with the 5G allele in stimulated MCs. The molecular mechanism for the 4G allele-mediated higher PAI-1 expression is associated with greater binding of upstream stimulatory factor-1 to the E-box adjacent to the 4G site (E-4G) than to the E-5G. In summary, PAI-1 may play an important role in the pathogenesis of asthma. Further studies evaluating the mechanisms of PAI-1 action and regulation may lead to the development of a novel prognostic factor and therapeutic target for the treatment and prevention of asthma and other PAI-1-associated diseases. [source]

Accelerated plasminogen activator inhibitor may prevent late restenosis after coronary stenting in acute myocardial infarction

CLINICAL CARDIOLOGY, Issue 3 2003
Teruo Inoue M.D.
Abstract Background: Although acceleration of plasma plasminogen activator inhibitor-1 (PAI-1) level after emergent coronary angioplasty in acute myocardial infarction (AMI) has been documented, its pathophysiologic role is still unknown. Hypothesis: This study was designed to elucidate the role of PAI-1 in the development of restenosis after primary coronary stenting in AMI. Methods: We selected for this study 66 patients with AMI, who underwent primary coronary stenting for infarct-related coronary artery lesions in an emergent situation. In all patients, plasma PAI-1 level was measured at admission, and at 3 h, 24 h, 48 h, and 1 month after coronary stenting. Results: At admission, the PAI-1 level was equivalent in 24 patients who experienced restenosis and in 42 patients without restenosis (28 ± 4 vs. 29 ± 4 ng/ml). In patients with restenosis, the levels did not change during the course after coronary stenting. In patients without restenosis, however, the level significantly increased at 3 h (48 ± 9 ng/ml, p < 0.001), 24 h (42 ± 9, p < 0.01), and 48 h (38 ± 7, p < 0.05) after coronary stenting, and was restored to the level equivalent to that at admission (27 ± 2 ng/ml) 1 month after coronary stenting. The PAI-1 level at 3 h after coronary stenting in patients without restenosis was significantly higher (p < 0.05) than the level (33 ± 6 ng/ml) in patients with restenosis. Multiple logistic regression analysis indicated that the PAI-1 level 3 h after coronary stenting was an independent predictor of restenosis (Wald x2 = 3.826, p = 0.019, odds ratio 0.921, 95% confidence interval 0.866-0.961). Conclusion: Accelerated PAI-1 after coronary stenting in patients with AMI may protect against the development of late restenosis. [source]

Pregnancy outcome and fibrinolytic, endothelial and coagulation markers in women undergoing uterine artery Doppler screening at 23 weeks

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2009
B. J. HUNT
Summary.,Background:,Pre-eclampsia (PET) and/or fetal growth restriction (FGR) remain a major cause of maternal and fetal morbidity and mortality. In pregnancy, fibrinolysis is controlled by the maternal endothelium and placenta, both of which are central to the pathogenesis of PET/FGR. Clinically, uterine artery Doppler screening at 23 weeks is used to predict PET/FGR. An abnormal uterine artery Doppler finding is defined as early diastolic bilateral uterine artery notching (BN) in the waveform. However, about 50% of mothers with BN do not develop PET/FGR. Objectives:,We investigated fibrinolytic changes and uterine artery Doppler findings in the second trimester, and related them to pregnancy outcome; in particular assessing whether fibrinolytic markers could discriminate between normal and abnormal outcome in mothers with BN. Patients/methods:,Plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), plasminogen activator inhibitor-2 (PAI-2), plasmin-,2 antiplasmin (PAP), D-dimers and markers of endothelial dysfunction were measured with Doppler ultrasound at 23 weeks. Results:,Those with BN had decreased PAP and D-dimer levels, and raised PAI-1 and thrombomodulin levels. Mothers with BN and PET/FGR had significantly increased t-PA levels and reduced PAI-2 levels. Conclusions:,BN at 23 weeks of gestation is associated with increased PAI-1 levels. Within the BN group, mothers who developed PET/FGR had increased t-PA levels and decreased PAI-2 levels, although there was no net change in fibrinolysis as measured by D-dimer levels. No single fibrinolytic marker is helpful in determining pregnancy outcome in those with BN, but t-PA and PAI-2 are worthy of study in a multifactorial algorithm. [source]

Plasminogen activator inhibitor-1 predicts coronary in-stent restenosis of drug-eluting stents

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2008
K. M. KATSAROS
Summary. Background:,We tested the hypothesis that plasma levels of plasminogen activator inhibitor-1 (PAI-1) are influenced by percutaneous coronary intervention (PCI) with the implantation of drug eluting stents (DES) and are able to predict the occurrence of in-stent restenosis (ISR). Methods and results:,PAI-1 active antigen plasma levels were determined in 75 patients before and 24 h after PCI with DES implantation. Patients with ISR after six to eight months (16%) showed significantly lower PAI-1 plasma levels before PCI (ISR, 11.7 ± 8.1 ng mL,1; non-ISR, 22.8 ± 18.8 ng mL,1; P <0.05). PAI-1 levels in the lowest tertile were associated with a 9.5-fold increased risk of ISR, independent of clinical risk factors, angiographic or procedural characteristics, compared to the highest tertile (P < 0.05). The induced change of PAI-1 active antigen 24 h after PCI was significantly higher in patients with ISR (ISR, +5.6 ± 8.0 ng mL,1; non-ISR, ,3.2 ± 12.1 ng mL,1; P < 0.05) with positive correlation to late lumen loss (r = 0.30; P < 0.05).Conclusions:,ISR after DES implantation is significantly related to plasma levels of PAI-1 active antigen before and after PCI. If confirmed by larger multicenter studies, the determination of PAI-1 plasma levels might be clinically helpful in the identification of patients at high risk of developing of ISR, even after DES implantation. [source]

Plasminogen activator inhibitor-1 contributes to the deleterious effect of obesity on the outcome of thrombotic ischemic stroke in mice

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2007
N. NAGAI
Summary.,Background:,It is widely accepted that obesity is a risk factor for ischemic heart disease, but the association with stroke is less clear. Adipose tissue is an important source of plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of plasminogen activation. Objective:,To test the hypothesis that elevated PAI-1 levels associated with obesity negatively affect the outcome of thrombotic ischemic stroke. Methods:,Middle cerebral artery (MCA) occlusion was induced photochemically in mice with nutritionally induced or genetically determined obesity and their lean counterparts. Results:,The MCA occlusion time (to obtain complete occlusion) was significantly shorter in obese (nutritionally induced) than in lean wild-type (WT) C57Bl/6 mice, whereas the infarct size was significantly larger and intracranial hemorrhage (ICH) was enhanced (all P < 0.05). Similar observations were made in genetically obese ob/ob mice, as compared to lean WT littermates. In both strains, obesity was associated with markedly elevated circulating PAI-1 levels, probably originating from the fat tissue. In contrast, PAI-1-deficient lean and obese mice did not display significant differences in MCA occlusion time, infarct volume or ICH. Conclusions:,Plasminogen activator inhibitor-1 may play a functional role in the deleterious effect of obesity on the outcome of thrombotic ischemic stroke in mice. [source]

Insulin resistance status is an important determinant of PAI-1 levels in HIV-infected patients, independently of the lipid profile

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2004
G. De Larrañaga
[source]

Neointima formation and thrombosis after vascular injury in transgenic mice overexpressing plasminogen activator inhibitor-1 (PAI-1)

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2004
H. R. Lijnen
Summary., The controversial role of plasminogen activator inhibitor-1 (PAI-1) in neointima formation and restenosis was studied with the use of a vascular injury model in transgenic mice overexpressing murine PAI-1 (PAI-1 Tg) and in wild-type (WT) controls. Despite the high circulating PAI-1 levels in the PAI-1 Tg mice (52 ± 9.8 ng mL,1 vs. 0.76 ± 0.17 ng mL,1 in WT mice), no significant fibrin deposition was observed in non-injured femoral arteries of 8- to 12-week-old mice. Two weeks after severe electric injury, extensive and comparable fibrin deposition was observed in both genotypes, despite a significantly reduced in situ fibrinolytic activity in arterial sections of the PAI-1 Tg mice. The neointimal and medial areas were similar in WT and PAI-1 Tg mice, resulting in comparable intima/media ratios (e.g. 0.94 ± 0.25 and 1.04 ± 0.17 at the center of the injury). Nuclear cell counts in cross-sectional areas of the neointima of the injured region were also comparable in arteries from WT and PAI-1 Tg mice (224 ± 63, 233 ± 20), and the distribution pattern of ,-actin-positive smooth muscle cells was similar. These findings indicate that in a vascular injury model that induces extensive and persistent fibrin deposition in femoral arteries of mice, overexpression of PAI-1 does not affect neointima formation. [source]

Impact of acute cellular rejection on coagulation and fibrinolysis biomarkers within the immediate post-operative period in pediatric liver transplantation

PEDIATRIC TRANSPLANTATION, Issue 3 2010
Jun Mimuro
Mimuro J, Mizuta K, Kawano Y, Hishikawa S, Hamano A, Kashiwakura Y, Ishiwata A, Ohmori T, Madoiwa S, Kawarasaki H, Sakata Y. Impact of acute cellular rejection on coagulation and fibrinolysis biomarkers within the immediate post-operative period in pediatric liver transplantation. Pediatr Transplantation 2010:14: 396,376. © 2009 John Wiley & Sons A/S. Abstract:, We studied restoration of the coagulation and fibrinolysis system in pediatric patients following liver transplantation and biomarkers of blood coagulation and fibrinolysis for suspecting the occurrence of acute cellular rejection. Coagulation activity recovered rapidly within two days following transplantation, but it took approximately 21,28 days for full recovery of the coagulation and fibrinolysis factors synthesized in the liver. PAI-1 levels were significantly higher in patients at the time of acute cellular rejection compared with levels after control of AR, and levels on days 14 and 28 in patients without AR. Plasma protein C and plasminogen levels at the time of rejection were significantly lower than those on day 14 in patients without AR. Statistical analysis suggested that an increase in plasma PAI-1 at a single time point in the post-operative period is a reliable marker among the coagulation and fibrinolysis factors for suspecting the occurrence of acute cellular rejection. These data suggested that appropriate anticoagulation may be required for 14 days after liver transplantation in order to avoid vascular complications and measurement of plasma PAI-1 levels may be useful for suspecting the occurrence of acute cellular rejection in pediatric patients following liver transplantation. [source]

Favorable response of pediatric stem cell recipients to human protein C concentrate substitution for veno-occlusive disease

PEDIATRIC TRANSPLANTATION, Issue 1 2007
S. W. Eber
Abstract:, Plasminogen activator inhibitor 1 is known to be elevated in patients with hepatic VOD after intensive chemotherapy. To re-establish endogenous fibrinolysis and to inhibit thrombin formation, we used non-APC (zymogen) to normalize PAI-1 levels. As a consequence of thrombin formation inhibition and the consecutive inhibition of the coagulation cascade, this treatment is expected to reduce the elevated D-dimer level. Six pediatric stem cell recipients with moderate or severe VOD after busulfan or total body irradiation conditioning regimen are reported here who were therapy-refractory to defibrotide or rt-PA therapy. All patients had low levels of PC activity (16,39%). The administration of PC (60,240 IU/kg) led to a rapid and sustained rise in PC activity (target level >80%) with near normalization of prothrombin and partial thromboplastin time in all patients. Elevated PAI-1 levels declined. Five of the six patients showed a good clinical response with prompt resolution of clinical, sonographic, and laboratory signs of hepatic blood flow obstruction, while one patient with severe VOD, as well as concomitant liver GVHD and CMV disease, had a slow but detectable response to PC therapy. All patients survived. [source]

Relationship between elevated cerebrospinal fluid levels of plasminogen activator inhibitor 1 and neuronal destruction in patients with neuropsychiatric systemic lupus erythematosus

ARTHRITIS & RHEUMATISM, Issue 7 2009
Jakub Kwieci
Objective A homeostatic imbalance between coagulation and fibrinolysis might occur intrathecally in neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no published data on levels of fibrinolytic factors in the cerebrospinal fluid (CSF) of patients with NPSLE. The present study was undertaken to assess CSF levels of fibrinolytic molecules, including urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), D-dimer, and plasminogen activator inhibitor 1 (PAI-1), in SLE patients with clinically verified neuropsychiatric involvement and to compare these levels with those in SLE patients without neuropsychiatric involvement and in healthy subjects. Methods Levels of uPA, tPA, and PAI-1 were assessed in CSF from 94 patients with SLE (33 who had NPSLE, 56 who did not have NPSLE, and 5 who were positive for antiphospholipid antibody [not included in the NPSLE or non-NPSLE group]) and from 53 age-matched controls. Patients were evaluated clinically, with magnetic resonance imaging of the brain, analyses of neuronal/glial degradation products in CSF, and neuropsychiatric testing. Results In the group of patients with NPSLE, intrathecal PAI-1 levels were significantly elevated compared with levels in SLE patients without overt neuropsychiatric involvement (P < 0.05) and in healthy controls (P < 0.001). In contrast, intrathecal levels of uPA did not differ significantly. Intrathecal levels of PAI-1 correlated significantly with CSF levels of interleukin-6 (IL-6) (r = 0.34, P < 0.001) and IL-8 (r = 0.33, P < 0.001). Importantly, increased PAI-1 and D-dimer levels were observed in SLE patients who had pathologically elevated levels of glial fibrillary acidic protein, neurofilament triplet protein, and tau protein in CSF. Conclusion Intrathecal release of PAI-1 is increased in patients with NPSLE. This results in impaired fibrinolysis, which might contribute to neuronal and astrocytic damage in NPSLE. [source]

PAI-1 promoter 4G/5G genotype as an additional risk factor for venous thrombosis in subjects with genetic thrombophilic defects

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2000
Rafael Seguí
Impaired fibrinolysis as a result of increased plasminogen activator inhibitor-1 (PAI-1) levels in plasma is a common finding in patients with deep vein thrombosis (DVT). A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to influence the levels of PAI-1. The 4G allele was found to be associated with higher plasma PAI-1 activity (act), but contradictory results on the incidence of the 4G allele in DVT patients have been reported. The aim of this study was to analyse whether the PAI-1 promoter 4G/5G genotype increases the risk of venous thrombosis in subjects with thrombophilic defects, and to determine the distribution of the PAI-1 4G/5G genotype and its relation to plasma PAI-1 levels in 190 unrelated patients with DVT in comparison with a control group of 152 healthy subjects. No differences between the 4G/5G allele distribution in the DVT group (0·43/0·57) and in the control group (0·42/0·58) were observed. However, the presence of the 4G allele significantly increased the risk of thrombosis in patients with other thrombophilic defects. Significantly higher PAI-1 levels were observed in DVT patients than in the controls. Our results also showed significant differences in the plasma levels of PAI-1 antigen (ag) and PAI-1 act among the 4G/5G genotypes in DVT patients. A multivariate analysis revealed that, in the DVT group, PAI-1 ag levels were influenced by the 4G allele dosage, triglyceride levels and body mass index (BMI). The influence of the 4G allele dosage on PAI-1 levels was independent of the triglyceride levels and BMI. In the control group, no significant correlation between PAI-1 levels and 4G allele dosage was observed. In conclusion, the PAI-1 promoter polymorphism was found to have an influence on PAI-1 levels in DVT patients and on the risk of venous thrombosis in subjects with other genetic thrombophilic defects. [source]

Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node,negative breast carcinoma

CANCER, Issue 3 2004
Peggy Manders M.Sc.
Abstract BACKGROUND The ability of a solid tumor to grow and metastasize has a significant dependence on protease systems, such as the plasminogen activation system. The plasminogen activation system includes the urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1), among other molecules. Both uPA and PAI-1 are established prognostic factors for patients with breast carcinoma. In the current study, the authors investigated whether the complex of uPA with PAI-1 is also associated with the natural course of this malignancy. METHODS Cytosolic levels of uPA, PAI-1, and the uPA:PAI-1 complex were measured in tumor tissue from 576 patients with lymph node,negative invasive breast carcinoma using quantitative enzyme-linked immunosorbent assays. Patients did not receive adjuvant systemic therapy, and the median follow-up duration was 61 months (range, 2,187 months) after primary diagnosis. Correlations with well known clinicopathologic factors were assessed, and univariate and multivariate survival analyses were performed. RESULTS uPA:PAI-1 complex levels were positively associated with adverse histologic grade and inversely correlated with estrogen and progesterone receptor status. On univariate analysis, increased levels of the uPA:PAI-1 complex were found to be associated with reduced recurrence-free survival (RFS) and overall survival (OS) rates. On multivariate analysis, uPA:PAI-1 complex levels were found to be an independent predictor of OS (P = 0.039), but not RFS (P = 0.240). When uPA and PAI-1 levels were not included in the multivariate analysis, uPA:PAI-1 complex levels became a significant predictor of both RFS and OS (P = 0.029 and P = 0.007, respectively). CONCLUSIONS The results of the current study demonstrate that uPA:PAI-1 complex levels have prognostic value on univariate analysis. In addition, increased uPA:PAI-1 complex levels were significantly associated with poor OS on multivariate analysis. Increased uPA:PAI-1 complex levels were also significantly associated with reduced RFS rates after the exclusion of uPA and PAI-1 levels from the multivariate analysis model. Cancer 2004. © 2004 American Cancer Society. [source]