scholarly journals Alu-repeat polymorphism in the tissue plasminogen activator (t-PA) gene, seminal t-PA concentration, and male fertility impairment: A case-control study

2020 ◽  
Author(s):  
Lubna Hamid Tahtamouni ◽  
Mahmoud Nael Hamdan ◽  
Zainab Ali Al-Mazaydeh ◽  
Randa Mahmoud Bawadi ◽  
Majdoleen Sobhi Rammaha ◽  
...  
Keyword(s):  
Male Infertility ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Plasminogen ◽  
Alu Element ◽  
Alu Repeat ◽  
Infertile Group ◽  
Activator Inhibitor

Background: Tissue plasminogen activator (t-PA) is a protein involved in the fibrinolytic system that catalyzes the conversion of plasminogen into the active plasmin. The activity of t-PA is controlled by plasminogen activator inhibitor-1. t-PA has crucial functions during spermatogenesis. One polymorphism was reported for t-PA gene, either the presence of a 300-bp Alu-repeat (Alu+) or its absence (Alu−). Objective: The current work aimed at studying the association between Alu polymorphism in the t-PA gene and male infertility. Materials and Methods: Using polymerase chain reaction on genomic DNA isolated from the blood of 79 participants, a region polymorphic for Alu element insertion in t-PA gene was amplified. In addition, total t-PA concentration, plasminogen activator inhibitor-1/t-PA complex concentration, and t-PA activity in seminal plasma were measured by enzyme-linked immunosorbent assay. Results: The results indicate that the percentage of infertile participants (n = 50) who were homozygous for t-PA Alu insertion (Alu+/+), heterozygous Alu+/− or homozygous for t-PA Alu deletion (Alu−/−) did not change significantly (p = 0.43, 0.81, and 0.85, respectively) when compared with the control participants (n = 29). On the other hand, a significant decrease (p = 0.0001) of t-PA total concentration in seminal plasma was observed in the infertile group in comparison with the control group. However, the results indicate that there is no association between the t-PA Alu different genotypes and the total t-PA seminal concentration in the infertile group when compared to the control group (p = 0.63). Conclusion: Data obtained from the current study does not support an association between t-PA Alu polymorphism and t-PA seminal concentration or male infertility. Key words: Alu element, Male infertility, Semen, Spermatogenesis, t-PA.

scholarly journals Effect of Plasminogen Activator Inhibitor-1 and Tissue Plasminogen Activator Polymorphisms on Susceptibility to Type 2 Diabetes in Malaysian Subjects

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Zaid Al-Hamodi ◽  
Riyadh Saif-Ali ◽  
Ikram S. Ismail ◽  
Khaled A. Ahmed ◽  
Sekaran Muniandy
Keyword(s):  
Type 2 Diabetes ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Additive Models ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Plasminogen ◽  
Alu Repeat ◽  
Activator Inhibitor ◽  
Pai 1

Elevated activity of plasminogen activator inhibitor-1 (PAI-1) and decreased tissue plasminogen activator (tPA) activity are considered to be important risk factors for type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). The aim of this study was to investigate the association of the PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms with T2DM in Malaysian subjects. Serum insulin, coronary risk panel, plasma glucose, and PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms were studied in 303 T2DM subjects (227 with MetS and 76 without MetS) and 131 normal subjects without diabetes and MetS. Statistical analysis showed that the dominant and additive models of PAI-1 4G/5G polymorphism showed a weak association with T2DM without MetS (OR=2.35,P=0.045;OR=1.67,P=0.058). On the other hand, the recessive model of the tPA Alu-repeat I/D polymorphism showed an association with T2DM with MetS (OR=3.32,P=0.013) whereas the dominant and additive models of the tPA Alu-repeat I/D polymorphism were not associated with T2DM either with or without MetS.

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.

Relationship of Plasminogen Activator Inhibitor-1 Levels following Thrombolytic Therapy with rt-PA as Compared to Streptokinase and Patency of Infarct Related Coronary Artery

1999 ◽  
Vol 82 (07) ◽  
pp. 104-108 ◽  
Author(s):  
Franck Paganelli ◽  
Marie Christine Alessi ◽  
Pierre Morange ◽  
Jean Michel Maixent ◽  
Samuel Lévy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Thrombolytic Therapy ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Plasminogen Activator Inhibitor 1 ◽  
Vessel Patency ◽  
Activator Inhibitor ◽  
Pai 1

Summary Background: Type 1 plasminogen activator inhibitor (PAI-1) is considered to be risk factor for acute myocardial infarction (AMI). A rebound of circulating PAI-1 has been reported after rt-PA administration. We investigated the relationships between PAI-1 levels before and after thrombolytic therapy with streptokinase (SK) as compared to rt-PA and the patency of infarct-related arteries. Methods and Results: Fifty five consecutive patients with acute MI were randomized to strep-tokinase or rt-PA. The plasma PAI-1 levels were studied before and serially within 24 h after thrombolytic administration. Vessel patency was assessed by an angiogram at 5 ± 1days. The PAI-1 levels increased significantly with both rt-PA and SK as shown by the levels obtained from a control group of 10 patients treated with coronary angioplasty alone. However, the area under the PAI-1 curve was significantly higher with SK than with rt-PA (p <0.01) and the plasma PAI-1 levels peaked later with SK than with rt-PA (18 h versus 3 h respectively). Conversely to PAI-1 levels on admission, the PAI-1 levels after thrombolysis were related to vessel patency. Plasma PAI-1 levels 6 and 18 h after SK therapy and the area under the PAI-1 curve were significantly higher in patients with occluded arteries (p <0.002, p <0.04 and p <0.05 respectively).The same tendency was observed in the t-PA group without reaching significance. Conclusions: This study showed that the PAI-1 level increase is more pronounced after SK treatment than after t-PA treatment. There is a relationship between increased PAI-1 levels after thrombolytic therapy and poor patency. Therapeutic approaches aimed at quenching PAI-1 activity after thrombolysis might be of interest to improve the efficacy of thrombolytic therapy for acute myocardial infarction.

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 THE FIBRINOLYTIC ALTERATION ASSOCIATED WITH DAILY ADMINISTRATION OF SILDENAFIL

2018 ◽  
Vol 11 (8) ◽  
pp. 107
Author(s):  
Fathelrahman M Hassan
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Daily Administration ◽  
Control Group ◽  
Average Weight ◽  
Plasminogen Activator Inhibitor 1 ◽  
Control Groups ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
D Dimer

Objective: The objective of this study was to determine the fibrinolytic alteration associated with daily administration of sildenafil.Methods: A total of 12 adult male rabbits without mortality rate had been fed standard and subdivided into four groups; their average weight was 1.5, 2.5, 1.9, and 2 kg randomly selected during the period of March 2012–July 2013. Depending on weight, the control groups (2.25 mg/1.5 kg day) and sildenafil groups (3 mg/2 kg/day, 2.85 mg/1.9 kg/day, and 1.7 mg/2.5 kg/day) were injected by normal saline and sildenafil concentration, respectively to create four groups, every group was composed of three rabbits; saline rabbit (control group, n=3) and sildenafil rabbits (sildenafil group, n=9). All rabbit’s plasma samples have been investigated for prothrombin time, activated partial thromboplastin time, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1+2, tissues plasminogen activator (tPA), plasmin antiplasmin (PAP), plasminogen, and D-dimer after 24 h of administration.Results: The PAP level was significantly (p<0.05) decreased following sildenafil injection. Sildenafil-injected (3 mg/ml) rabbits had decreased the means of PAI-1 and mean tPA, as early as 1-day post-injection, with a considerable lower PAP first determined 3 days after injection that continued into each rabbit 2 and 3.Conclusion: Better strategies are to initiate and manipulate this drug ought to reduce the chance of each thrombosis and hemorrhage, at the same time as minimizing the need for laboratory monitoring with the aid of the use of PAI-1, tPA, and PAP checks.

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