scholarly journals Association of Polymorphisms in Plasminogen Activator Inhibitor-1 (PAI-1), Tissue Plasminogen Activator (tPA), and Renin (REN) with Recurrent Pregnancy Loss in Korean Women

2021 ◽  
Vol 11 (12) ◽  
pp. 1378
Author(s):  
Hee Young Cho ◽  
Han Sung Park ◽  
Eun Hee Ahn ◽  
Eun Ju Ko ◽  
Hyeon Woo Park ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Plasminogen Activator Inhibitor ◽  
Endocrine Disorders ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Plasminogen ◽  
Activator Inhibitor ◽  
Pai 1

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestational age. Various factors, including immune dysfunction, endocrine disorders, coagulation abnormality, and genetic disorders influence RPL. In particular, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), and renin (REN) have important roles in the thrombotic and thrombolytic systems, and abnormal expression of these genes have a reported negative correlation with pregnancy maintenance. Moreover, some polymorphisms of the three genes are related to expression levels and thrombotic disorder. Therefore, we investigated whether polymorphisms of PAI-1, tPA, and REN are linked to RPL. Genotyping of the six polymorphisms (PAI-1 rs11178, rs1050955, tPA rs4646972, rs2020918, REN rs1464816, and rs5707) was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and associations of the polymorphisms with RPL were evaluated by statistical analysis. The polymorphism PAI-1 rs1050955 GA+AA was associated with decreased RPL risk (AOR, 0.528; 95% CI 0.356–0.781; p = 0.001) as was the REN 10795 rs5707 GG genotype (AOR, 0.487; 95% CI 0.301–0.787; p = 0.003). In contrast, the tPA rs4646972 II genotype correlated with increased RPL risk (AOR, 1.606; 95% CI, 1.047–2.463; p = 0.030). This study provides evidence that tPA Alu rs4646972 may contribute to the risk of idiopathic RPL, but PAI-1 12068 rs1050955 and REN 10795 rs5707 are associated with a decreased risk of RPL. Therefore, these alleles may be useful as biomarkers to evaluate the risk of RPL.

scholarly journals The mechanism of the reaction between human plasminogen-activator inhibitor 1 and tissue plasminogen activator

1990 ◽  
Vol 265 (1) ◽  
pp. 109-113 ◽  
Author(s):  
T L Lindahl ◽  
P I Ohlsson ◽  
B Wiman
Keyword(s):  
Amino Acid ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Peptide Bond ◽  
Plasminogen Activator Inhibitor 1 ◽  
Sds Page ◽  
Tissue Plasminogen ◽  
Activator Inhibitor ◽  
Pai 1

The structural events taking place during the reaction between PAI-1 (plasminogen-activator inhibitor 1) and the plasminogen activators sc-tPA (single-chain tissue plasminogen activator) and tc-tPA (two-chain tissue plasminogen activator) were studied. Complexes were formed by mixing sc-tPA or tc-tPA with PAI-1 in slight excess (on an activity basis). The complexes were purified from excess PAI-1 by affinity chromatography on fibrin-Sepharose. Examination of the purified complexes by SDS/polyacrylamide-gel electrophoresis (SDS/PAGE) and N-terminal amino acid sequence analysis demonstrated that a stoichiometric 1:1 complex is formed between PAI-1 and both forms of tPA. Data obtained from both complexes revealed the amino acid sequences of the parent molecules and, in addition, a new sequence: Met-Ala-Pro-Glu-Glu-. This sequence is found in the C-terminal portion of the intact PAI-1 molecule and thus locates the reactive centre of PAI-1 to Arg346-Met347. The proteolytic activity of sc-tPA is demonstrated by its capacity to cleave the ‘bait’ peptide bond in PAI-1. The complexes were inactive and dissociated slowly at physiological pH and ionic strength, but rapidly in aq. NH3 (0.1 mol/l). Amidolytic tPA activity was generated on dissociation of the complexes, corresponding to 0.4 mol of tPA/mol of complex. SDS/PAGE of the dissociated complexes indicated a small decrease in the molecular mass of PAI-1, in agreement with proteolytic cleavage of the ‘bait’ peptide bond during complex-formation.

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

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.

scholarly journals Coagulopathy is Initiated with Endothelial Dysfunction and Disrupted Fibrinolysis in Patients with COVID-19

2021 ◽  
Author(s):  
FATMA BURCU BELEN APAK ◽  
Gulbahar Yuce ◽  
Deniz Ilhan Topcu ◽  
Ayse Gultekingil ◽  
Yunus Emre Felek ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Endothelial Protein C Receptor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Plasminogen ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Background: A substantial group of patients suffer coagulopathy of Covid-19 (CAC) and are presented with thrombosis. The pathogenesis involved in CAC is not fully understood.Objectives: We evaluated the hemostatic and inflammatory parameters of 51 hospitalized Covid-19 adult patients and 21 controls. The parameters analyzed were danger signal molecule (High molecular weight group box protein-1/HMGBP-1), platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, fibrinogen, endothelial protein C receptor (EPCR), soluble E-selectin, soluble P-selectin, thrombomodulin, tissue plasminogen activator (TPA), plasminogen activator inhibitor-1 (PAI-1), soluble fibrin monomer complex (SFMC), platelet-derived microparticles (PDMP), β-thromboglobulin, antithrombin and protein C. The main objective of our study was to investigate which part of the hemostatic system was mostly affected at the admission of Covid-19 patients and whether these parameters could differentiate intensive care unit (ICU) and non-ICU patients. Patients and Methods:In this prospective case-control study, 51 patients ≥18 years who are hospitalized with the diagnosis of Covid-19 and 21 healthy control subjects were included. We divided the patients into two groups according to their medical progress, either into ICU and non-ICU group. Regarding the outcome, patients were again categorized as survivor and non-survivor groups. Blood samples were collected from patients at admission at the time of hospitalization before administration of any treatment for Covid-19. The analyzes of the study were made with the IBM SPSS V22 program. p < 0.05 was considered statistically significant.Results:A total of 51 adult patients (F/M: 24/27) (13 ICU and 38 non-ICU) were included in the study cohort. The mean age of the patients was 68.1 ± 14.4 years. The control group consisted of 21 age and sex-matched healthy individuals. All of the patients were hospitalized, in a group of 13 patients, Covid-19 progressed to severe form and were hospitalized at ICU. We found out that the levels of fibrinogen, prothrombin time (PT), endothelial protein-C receptor (EPCR), D-dimer, soluble E-selectin, soluble P-selectin, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (TPA) were increased; whereas, the levels of soluble fibrin monomer complex (SFMC), platelet-derived microparticles (PDMP), antithrombin and protein-C were decreased in Covid-19 patients compared to the control group at hospital admission. Tissue plasminogen activator was the only marker that had a significantly different median level between ICU and non-ICU groups (p<0.001).Conclusions:In accordance with the previous literature, we showed that Covid-19 associated coagulopathy is distinct from sepsis-induced DIC with prominent early endothelial involvement and fibrinolytic shut-down. Reconstruction of endothelial function at early stages of infection may protect patients to progress to ICU hospitalization. We believe that after considering the patient’s bleeding risk, early administration of LMWH therapy at Covid-19 even in at outpatient setting may be useful both for restoring endothelial function and anticoagulation. The intensity of anticoagulation in non-ICU and ICU Covid-19 patients should be clarified with further studies.

Genetic association of five plasminogen activator inhibitor-1 (PAI-1) polymorphisms and idiopathic recurrent pregnancy loss in Korean women

2013 ◽  
Vol 110 (10) ◽  
pp. 742-750 ◽  
Author(s):  
Bo Eun Lee ◽  
Yi Seul Choi ◽  
Ji Hyang Kim ◽  
Ji Eun Shin ◽  
HyungChul Rah ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Plasminogen Activator Inhibitor ◽  
Korean Women ◽  
Plasminogen Activator Inhibitor 1 ◽  
Ordinal Logistic Regression Analysis ◽  
Polymerase Chain ◽  
Activator Inhibitor ◽  
Pai 1

SummaryPlasminogen activator inhibitor-1 (PAI-1) is important for maintaining pregnancy. Aberrantly increased PAI-1 levels may contribute to thrombosis and inflammation, leading to pregnancy loss. This study investigated the association of PAI-1 polymorphisms (PAI-1 rs2227631 [-844G>A], rs1799889 [-675 4G/5G], rs6092 [43G>A], rs2227694 [9785G>A], and rs7242 [11053T>G]) with idiopathic recurrent pregnancy loss (RPL) in Korean women. We screened 308 RPL patients and 227 control participants for five PAI-1 polymorphisms. Genotyping of PAI-1 was performed by polymerase chain reaction-restriction fragment length polymorphism assay. PAI-1 4G4G and -844AA/ 4G4G/11053GG genotypes were associated with RPL. PAI-1 -844A/4G/43G/9785G/11053G haplotype was connected to hypofibrinolytic status (i.e. increased levels of plasma PAI-1, increased numbers of platelets, reduced prothrombin time, and reduced activated partial thromboplastin time). Moreover, PAI-1 11053TG+GG frequency was positively related to plasma homocysteine and urate levels, whereas -844AA frequency was associated with plasma folate concentrations according to ordinal logistic regression analysis. Based on these results, we propose that PAI-1 -844G>A, 4G/5G, and 11053T>G polymorphisms are markers of RPL.

scholarly journals Testosterone does not adversely affect fibrinogen or tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) levels in 46 men with chronic stable angina

2005 ◽  
Vol 152 (2) ◽  
pp. 285-291 ◽  
Author(s):  
A M Smith ◽  
K M English ◽  
C J Malkin ◽  
R D Jones ◽  
T H Jones ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Stable Angina ◽  
Chronic Stable Angina ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Bioavailable Testosterone ◽  
Tissue Plasminogen ◽  
Activator Inhibitor ◽  
Pai 1

Objective: In women, sex hormones cause increased morbidity and mortality in patients with coronary heart disease (CHD) and adversely affect the coagulation profile. We have studied the effect of physiological testosterone replacement therapy in men on coagulation factor expression, to determine if there is an increased risk of thrombosis. Methods: Double-blind, randomized, placebo-controlled trial of testosterone in 46 men with chronic stable angina. Measurements of free, total and bioavailable testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH), estradiol, plasminogen activator inhibitor-1 (PAI-1), fibrinogen, tissue plasminogen activator (tPA) and full blood count were made at 0, 6 and 14 weeks. Results: Bioavailable testosterone levels were: 2.58 ± 0.58 nmol/l at baseline, compared with 3.35 ± 0.31 nmol/l at week 14 (P < 0.001) after treatment compared with 2.6 ± 0.18 nmol/l and 2.44 ± 0.18 nmol/l in the placebo group (P was not significant). There was no change in fibrinogen (3.03 ± 0.18 g/l at baseline and 3.02 ± 0.18 g/l at week 14, P = 0.24), tPA activity (26.77 ± 4.9 Iu/ml and 25.67 ± 4.4 Iu/ml, P = 0.88) or PAI-1 activity (0.49 ± 0.85 Iu/ml and 0.36 ± 0.06 Iu/ml, P = 0.16) with active treatment and no differences between the groups (at week 14, P value 0.98, 0.59 and 0.8 for fibrinogen, PAI-1 and tPA respectively). Haemoglobin concentration did not change over time, in the testosterone group (1.44 ± 0.02 g/l and 1.45 ± 0.02 g/l, P = 0.22). Conclusion: Physiological testosterone replacement does not adversely affect blood coagulation status.

Tissue Plasminogen Activator (t-PA) and Plasminogen Activator Inhibitor-1 (PAI-1) in Essential Thrombocythemia and Polycythemia Vera and Thrombotic Complications.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4879-4879
Author(s):  
Rossella R. Cacciola ◽  
Ernesto Di Francesco ◽  
Rosario Giustolisi ◽  
Emma Cacciola
Keyword(s):  
Polycythemia Vera ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Essential Thrombocythemia ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Plasminogen ◽  
Thrombotic Complications ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Thrombotic complications are frequent in patients with essential thrombocythemia (ET) and polycythemia vera (PV). While a thrombin- and tissue plasminogen activator (t-PA)-regulated release of t-PA and plasminogen activator inhibitor-1 (PAI-1), respectively, has been shown and an association between elevated t-PA and PAI-1 and thrombogenesis has been studied for several vascular diseases, few studies have concentrated on the correlation between t-PA and PAI-1 levels and thrombogenesis in these myeloproliferative disorders. Therefore, we investigated prothrombin fragment 1+2 (F1+2), as marker of thrombin generation, and t-PA and PAI-1 in patients with ET and PV and thrombosis. We included 44 patients, 22 ET (5 men and 17 women, mean age 55 years) and 22 PV (17 men and 5 women, mean age 60 years) who fulfilled PVSG. The mean duration of disease was 4.5 years. Most received cytoreduction, such as hydroxyurea (13 ET and 14 PV), interferon-alpha (2 ET), anagrelide hydrochloride (5 ET) or phlebotomy (8 PV). None of studied patients had thrombotic risk factors. Of 44 patients, 25 (12 ET and 13 PV) developed thrombosis, whereas 19 (10 ET and 9 PV) did not. Measurements were assayed by ELISA. All patients had increased F1+2 (2.8±2.8 nmol/L vs 0.7±0.2 nmol/L) (p=0.001). t-PA and PAI-1 were higher in those patients with previous thrombosis than in asymptomatic patients (130±62 ng/ml vs 89±69 ng/ml and 45±20 ng/ml vs 57±27 ng/ml, respectively) (p=0.043 and p=0.085, respectively). A positive correlation there was between F1+2 and t-PA and t-PA and PAI-1 (p<0.0001 and p<0.0001, respectively). These findings suggest that a disfibrinolysis may be in ET and PV and that t-PA and PAI-1 may be predictive additional factors of the thrombotic tendency of these patients.

scholarly journals Inhibition of tissue plasminogen activator activity by aspirin in vivo and its relationship to levels of tissue plasminogen activator inhibitor antigen, plasminogen activator and their complexes

Blood ◽  
1989 ◽  
Vol 74 (5) ◽  
pp. 1635-1643 ◽  
Author(s):  
RI Levin ◽  
PC Harpel ◽  
JG Harpel ◽  
PA Recht
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Plasminogen Activator Inhibitor 1 ◽  
Subsequent Formation ◽  
Tissue Plasminogen ◽  
Plasmin Inhibitor ◽  
Activator Inhibitor ◽  
Pai 1

Abstract The observation that aspirin inhibits the increment in tissue plasminogen activator (t-PA) activity induced by venous occlusion of the forearm became controversial with the publication of several nonconfirmatory studies. The current study was performed to confirm the original observation and determine the mechanism by which aspirin suppresses the incremental t-PA activity induced by venous occlusion. Aspirin (650 mg/d X 2) caused no change in resting levels of t-PA antigen (t-PA:Ag) or activity, plasminogen activator inhibitor 1 antigen (PAI-1:Ag), or activity or t-PA-PAI-1 complexes. In contrast, aspirin reduced the increments induced by venous occlusion as follows: t-PA:Ag by 45% (P = .001); t-PA activity (euglobulin lysis time, ELT) by 43% (P = .006); and t-PA activity (alpha 2-plasmin inhibitor-plasmin complexes, PIPC) by 41% (P = .003). The inhibition of incremental t-PA activity measured as ELT or PIPC was linearly correlated with the inhibition of incremental t-PA:Ag (respectively, r = .75, P less than .02; r = .67, P less than .05). Aspirin had no effect on the increment in PAI-1:Ag induced by venous occlusion, but similar to the effect on t- PA:Ag, aspirin induced a 51% inhibition of the increment in t-PA-PAI-1 complex formation. Aspirin did not alter the ability of alpha 2-plasmin inhibitor to bind plasmin, nor the ability of plasma to support the fibrin-catalyzed generation of plasmin by t-PA, nor the subsequent formation of PIPC. Aspirin inhibits the t-PA activity induced by venous occlusion primarily by inhibiting the release of t-PA antigen.

scholarly journals Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in serbian population

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Ivana Joksic ◽  
Zeljko Mikovic ◽  
Dejan Filimonovic ◽  
Jelena Munjas ◽  
Natasa Karadzov Orlic ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Gene Polymorphisms ◽  
Factor Xiii ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
History Of ◽  
Activator Inhibitor ◽  
Pai 1

SummaryBackgroundRecurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one of the causes of RPL. Here we examined the prevalence of nine thrombophilic gene polymorphisms among women with history of recurrent miscarriages and fertile controls.MethodsThe study included 70 women with history of at least three early pregnancy losses and 31 fertile controls with no miscarriages. We investigated mutations in genes responsible for clotting and fibrinolysis, including factor V (FV) Leiden, FV H1299R, factor II (FII) G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor (EPCR) H1 and H3 haplotypes using reverse polymerase chain reaction ViennaLab cardiovascular disease StrippAssays.ResultsOur results showed no significant increase in prevalence of tested polymorphisms in women with RPL. However, relative risk for PRL among women heterozygous for FXIII V34L was 2.81 times increased (OR 2.81, 95% CI 1.15–6.87, P=0.023). Haplotype analysis showed that combined presence of high-risk genotypes for FXIII and PAI-1 significantly increases risk for RPL (OR 13.98, CI 95% 1.11–17.46, P=0.044).ConclusionsThis is the first study in Serbian population that investigated prevalence of FVR2, A1298C, FXIII V34L and EPCR gene variants. Compound heterozygosity for FXIII V34L and PAI-1 4G is significant risk factor for recurrent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings.

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