Experimental Study of Fibrinolytic Factors and Its Inhibitors in Rabbits’ Tissues Extract.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3965-3965
Author(s):  
Xiaohua Xu ◽  
Liansheng Huang ◽  
Xingguo Lu ◽  
Genbo Xu ◽  
Xiaoying Zhao
Keyword(s):  
Small Intestine ◽  
Cardiac Muscle ◽  
High Activity ◽  
Plasminogen Activator ◽  
Large Intestine ◽  
Renal Cortex ◽  
Activity Levels ◽  
Striped Muscle ◽  
Significant Difference ◽  
Pai 1

Abstract Objective: To study the expression character of fibrinolytic factors and its inhibitors in rabbits’ tissues extract. Methods: Tissue plasminogen activator ( tPA ), Plasminogen activator inhibitor-1 ( PAI-1 ), Plasminogen ( Plg ), Plasmin ( Pl ) and α2 Plasmin inhibitor ( α2PI ) were measured by colorimetric assay. Results: The tissues extract in renal, small intestine, lung, brain and spleen showed strong fibrinolytic function, and expressed markedly high activity levels of tPA, Plg and Pl. But striped muscle, tongue and stomach expressed markedly high activity levels of PAI-1 and α2PI, and showed low fibrinolytic character. There were linear correlation between levels of tPA and PAI-1 ( r=−0.8076, P<0.01 ), Pl and αPI ( r=−0.3278, P<0.05 ), Plg and Pl ( r=0.6811, P<0.01 ) in tissues extract fibrinolytic targets. In relative tissues, renal cortex and renal marrow were significantly high level of tPA and low level of PAI-1, but levels of Plg and Pl in cortex renalis were higher than in renal marrow, the α 2PI level in renal marrow were higher than in renal cortex ( P<0.05~0.01 ). The levels of tPA, Plg and Pl in small intestine were higher than tin large intestine ( P<0.05~0.01 ), but the levels of PAI-1 and α 2PI in small intestine were markedly lower than in large intestine ( P<0.01 ). These indicated that fibrinolytic function in small intestine was stronger than in large intestine. Although the fibrinolytic function in muscle tissue was low, but the levels of tPA, Plg, and Pl in cardiac muscle were obviously higher than in striped muscles, and the levels of PAI-1 and α 2PI were obviously lower than in striped muscle ( P<0.05~0.01 ). These indicated that the fibrinolytic function in cardiac muscle were stronger than in the striped muscle. Conclusion: The fibrinolytic character existed significant difference in tissues, it has profound significance in the function of heamostasis and thrombosis and physiologic function in tissues.

A Specific Immunologic Assay for Functional Plasminogen Activator Inhibitor 1 in Plasma – Standardized Measurements of the Inhibitor and Related Parameters in Patients with Venous Thromboembolic Disease

1992 ◽  
Vol 68 (05) ◽  
pp. 486-494 ◽  
Author(s):  
Malou Philips ◽  
Anne-Grethe Juul ◽  
Johan Selmer ◽  
Bent Lind ◽  
Sixtus Thorsen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Normal Subjects ◽  
Tissue Type ◽  
Blood Collection ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Significant Difference ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-l complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.

Immunoreactivity of Tissue Plasminogen Activator and of Its Inhibitor Complexes

1989 ◽  
Vol 61 (03) ◽  
pp. 409-414 ◽  
Author(s):  
M Rånby ◽  
G Nguyen ◽  
P Y Scarabin ◽  
M Samama
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Degradation Products ◽  
Gel Filtration ◽  
Free Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasma Samples ◽  
Significant Difference ◽  
Tissue Plasminogen ◽  
Pai 1

SummaryAn enzyme linked immunosorbent assay (ELISA) based on goat polyclonal antibodies against human tissue plasminogen activator (tPA) was evaluated. The relative immunoreactivity of tPA in free form and tPA in complex with inhibitors was estimated by ELISA and found to be 100, 74, 94, 92 and 8l% for free tPA and tPA in complex with PAI-1, PAI-2, α2-antiplasmin and C1-inhibitor, respectively. Addition of tPA to PAI-1 rich plasma resulted in rapid and total loss of tPA activity without detectable loss of ELISA response, indicating an immunoreactivity of tPA in tPA/PAI-1 complex of about l00%. Three different treatments of citrated plasma samples (acidification/reneutralization, addition of 5 mM EDTA or of 0.5 M lysine) prior to determination by ELISA all resulted in increased tPA levels. The fact that the increase was equally large in all three cases along with good analytical recovery of tPA added to plasffi, supported the notion that all tPA antigen present in plasma samples is measured by the ELISA. Analysis by ELISA of fractions obtained by gel filtration of plasma from a patient undergoing tPA treatment identified tPA/inhibitor complexes and free tPA but no low molecular weight degradation products of tPA. Determinations of tPA antigen were made at seven French clinical laboratories on coded and randomized plasma samples with known tPA antigen content. For undiluted samples there was no significant difference between the tPA levels found and those known to be present. The between-assay coefficient of variation was 7 to 10%. In conclusion, the ELISA appeared suited for determination of total tPA antigen in human plasma samples.

Abstract 267: A Single Dose of Reconstituted High Density Lipoprotein Reduces Expression of Tissue-Factor In Human Carotid Atherosclerotic Plaques

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Hosaam H Nasr ◽  
Ian M Loftus ◽  
Saiqa Sayed ◽  
Alun Jones ◽  
Evelyn Torsney ◽  
...  
Keyword(s):  
Single Dose ◽  
Tissue Factor ◽  
Plasminogen Activator ◽  
Clinical Event ◽  
Tissue Type ◽  
Transcriptional Level ◽  
Rt Pcr ◽  
Significant Difference ◽  
Plaque Stabilisation ◽  
Pai 1

Background: Multiple infusions of HDLs have been shown to mediate approximately 4% reduction in plaque volume. This may relate to removal of intra-plaque lipid, but the precise mechanism is unknown. To test the hypothesis that HDLs may influence plaque stabilisation through modulating transcription, we examined the effects of a single dose of rHDL on expression of thrombomodulatory genes in carotid plaques. Materials and Methods: Forty patients undergoing carotid endarterectomy (CEA) were stratified to three groups: early symptomatics ( n =12, stroke/transient ischemic attack (TIA) 1month before CEA)late symptomatics ( n =14, stroke/TIA > 1month before CEA); and asymptomatics ( n =12). RNA was isolated from plaques following CEA, and expression of the thrombomodulatory genes, tissue factor (TF); tissue factor pathway inhibitor (TFPI); thrombomodulin (TM); tissue type plasminogen activator (tPA); urokinase plasminogen activator (uPA); plasminogen activator inhibitor-1 (PAI-1), measured using QRT-RT-PCR. Nine patients with early symptomatic carotid disease, undergoing CEA, were then randomised to infusion of reconstituted HDL (rHDL) 80mg/kg Apo A-I ( n =4) or a similar volume of phosphate buffered saline ( n =5). Plaque specimens were collected 24 hrs later and RNA isolated for QRT-RT- PCR measurement of thrombomodulatory gene expression. Results: A significant difference in TF, TM, tPA and PAI-1 genes were observed in the 3 patient groups (see Table 1 ). In the rHDL group, a single dose of rHDL reduced the expression of TF (0.71 (0.65–0.75) vs 0.98 (0.81–1.14), P=0.05). No significant difference was observed in other thrombomodulatory factors between the 2 groups. Conclusions: Plaque stabilisation, which occurs within one month of a clinical event may be facilitated, at the transcriptional level, following rHDL infusion. We hope to report a larger double blind placebo controlled trial which will determine the full effects of rHDLs on plaque stability. Table 1

Sex Differences in the Determinants of Fibrinolytic Activity

1998 ◽  
Vol 79 (03) ◽  
pp. 587-590 ◽  
Author(s):  
J. A. Cooper ◽  
D. J. Howarth ◽  
T. W. Meade ◽  
G. J. Miller ◽  
P. K. MacCallum
Keyword(s):  
Plasminogen Activator ◽  
Whole Blood ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Clot Lysis ◽  
Significant Difference ◽  
Main Determinants ◽  
Activator Inhibitor Type ◽  
Pai 1

SummaryImpaired whole blood fibrinolytic activity (FA), measured by the dilute clot lysis time (DCLT), is associated with first episodes of ischaemic heart disease (IHD) in the Northwick Park Heart Study in men, especially under 55 years, and in women. In a community-based study to investigate possible determinants of the DCLT, and therefore to assess which fibrinolytic components might be predictors of first IHD events, we measured fibrinolytic variables in a sub-sample of 150 healthy adults (73 males, 77 females) randomly selected from a single general practice.Most of the variance in DCLT (68% in men, 63% in women) was explained by tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) activities. In multiple regression analysis there was a significant difference in the strength of the association of t-PA activity with DCLT in men compared to women (test for interaction p = 0.05), the association of t-PA activity with DCLT being significant in males but not in females. Plasma PAI-1 activity was strongly associated with DCLT in both sexes. There was no independent association of DCLT with plasma fibrinogen, t-PA antigen, other fibrinolytic inhibitors, body mass index, serum lipids or C-reactive protein.Plasma PAI-1 activity in females and both t-PA and PAI-1 activities in males are the main determinants of whole blood FA measured by DCLT. It is therefore likely that these modulators of the plasma fibrinolytic system are associated with the onset of first clinical episodes of IHD. Elevated levels of t-PA antigen were positively associated with DCLT after adjustment for age and sex and therefore indicate impaired rather than enhanced FA. Further studies of the association of FA with risk of IHD should include not only “global” measures but also assessment of t-PA and PAI-1 activities, particularly as our results suggest that their associations with IHD may differ in men and women.

scholarly journals Is There a Tendency for Thrombosis in Gestational Diabetes Mellitus?

2016 ◽  
Vol 8 (02) ◽  
pp. 101-105 ◽  
Author(s):  
Suheyla Gorar ◽  
Bulent Alioglu ◽  
Esranur Ademoglu ◽  
Seyit Uyar ◽  
Handan Bekdemir ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Study Groups ◽  
Tissue Type ◽  
Coagulation System ◽  
Significant Difference ◽  
Pai 1

ABSTRACT Context: Impact of gestational diabetes mellitus (GDM) on the coagulation system, dynamics involved at a pathophysiological level and the exact mechanism remain unclear. Aims: To evaluate the association between diabetes-related parameters and hemostatic factors to search for a tendency of thrombosis in GDM. Settings and Design: Nineteen pregnant women who had GDM, 16 healthy pregnant and 13 healthy nonpregnant controls admitted to the Endocrinology outpatient clinics were enrolled in the study. Subjects and Methods: Fasting and postprandial glucose, hemoglobin A1c and insulin levels, and insulin resistance; fructosamine, thrombin activatable fibrinolysis inhibitor (TAFI), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor Type-1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, plasminogen and hemoglobin levels, platelet counts, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were studied. Statistical Analysis Used: One-way analysis of variance, Kruskal–Wallis, and post hoc Tukey honestly significant difference or Conover’s nonparametric multiple comparison tests for comparison of the study groups. Results: PT and aPTT were significantly lower in GDM patients compared to controls (P < 0.05), whereas fibrinogen and plasminogen levels were significantly higher in this group compared to both nonpregnant and healthy pregnant controls (P < 0.05 for each). TAFI, TFPI, PAI-1, and tissue t-PA levels were not significantly different among groups. Conclusions: Our findings indicate tendency to develop thrombosis in GDM similar to diabetes mellitus; but more comprehensive studies with larger sample size are needed to determine the relationship between GDM and hemostasis.

Differences Between Upper and Lower Limbs in Venous Endothelial Reactivity in Humans

1994 ◽  
Vol 9 (1_suppl) ◽  
pp. 10-14
Author(s):  
O. Bailliart ◽  
L. Boudaoud ◽  
Ph. Bonnin ◽  
C. Bal Dit Sollier ◽  
J. Roussi ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Plasminogen Activator ◽  
Plasma Concentrations ◽  
Cell Activity ◽  
Lower Limbs ◽  
Cell Recovery ◽  
Significant Difference ◽  
Cell Release ◽  
The Right ◽  
Pai 1

Objective: To determine the variability of endothelial reactivity to venostasis in the upper and lower limbs of healthy subjects. Participants: Ten healthy volunteers were investigated twice, at an interval of 1-week. Main outcome measures: Plasma concentrations of substances released from endothelial cells were determined in each limb after 10 min of venostasis in a sequential manner. Tissue plasminogen activator (tPA), plasminogen activator inhibiting factor (PAI-1), thrombin–antithrombin complexes (TAT) and D-dimers (D-Di) were used as indicators of the thrombotic process and its reactions; angiotensin converting enzyme (ACE) and endothelin-1 (ET1) were related to endothelial cell activity involved in vascular tone regulation. Results: No difference was observed in endothelial cell recovery following venostasis after an interval of 1 week. A significant difference in endothelial cell release was found between the upper and lower limbs and between the right and left legs. Conclusions: Excellent reproducibility of measurements was observed. In keeping with the higher frequency of venous thrombosis in the lower limbs, the left leg seemed to be less reactive after venostasis, and the endothelium was more reactive in the upper than in the lower limbs.

Multicentre Evaluation of Commercial Kit Methods: Plasminogen Activator Inhibitor Activity

1993 ◽  
Vol 70 (05) ◽  
pp. 852-857 ◽  
Author(s):  
J Gram ◽  
P J Declerck ◽  
J Sidelmann ◽  
J Jespersen ◽  
C Kluft
Keyword(s):  
Plasminogen Activator ◽  
Inverse Correlation ◽  
Plasminogen Activator Inhibitor ◽  
Mean Value ◽  
Activity Level ◽  
Activity Levels ◽  
Commercial Kits ◽  
Activator Inhibitor ◽  
Pai 1

SummaryIn order to study the analytical performance of different commercial kits for determination of plasminogen activator inhibitor (PAI) activity we distributed eight selected split samples to 11 European laboratories experienced with haemostasis testing. Three different laboratories were involved in the production of data from each of the commercial kits tested. A considerable variation of PAI activity results reported from the laboratories testing the same commercial kits was observed. The range of reported results could in individual samples exceed the median value indicating an interlaboratory variation of more than 100%.When we harmonized the results reported from different kits in different laboratories by means of an international standard from National Institute for Biological Standards and Control (NIBSC) we still observed that the results produced by some kits deviated systematically from results produced by other kits. Also, the harmonized results were used to estimate the overall coefficient of variation (CV) of PAI activity determined in various laboratories by different kits. We observed an inverse correlation between the PAI activity level and the CV with a CV of about 10Q% for low PAI activity levels and a CV of about 16% for high PAI activity levels. The high imprecision of the kits in the low concentration range of PAI activity indicates that unspecific factors in plasma may interfere with determination of active PAI. This was confirmed by the evaluation of the results from one of the plasma samples, which was PAI-1 depleted. The laboratories involved in the testing reported for this sample a mean value of 6.1 IU/ml.In conclusion, the currently available kits for determination of PAI activity are not accurate for measurement of PAI-1 in plasma, and the kits give imprecise results particularly at low activity levels.

Microparticle-linked tissue factor activity and increased thrombin activity play a potential role in fibrinolysis failure in ST-segment elevation myocardial infarction

2009 ◽  
Vol 101 (04) ◽  
pp. 734-740 ◽  
Author(s):  
Nadine Ajzenberg ◽  
Laurent Feldman ◽  
Marie-Claude Guillin ◽  
Philippe Gabriel Steg ◽  
Marie-Geneviève Huisse
Keyword(s):  
Tissue Factor ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Platelet Glycoprotein ◽  
Factor Activity ◽  
St Segment Elevation ◽  
Tissue Factor Activity ◽  
St Segment ◽  
Significant Difference ◽  
Pai 1

SummaryFibrinolysis for acute ST-segment elevation MI achieves early recanalisation of the infarct artery in approximately 60% of cases. The aim of the study was to determine whether failure to achieve recanalisation was associated with differences in haemostasis biomarkers compared to patients with successful fibrinolysis. Fourty-three patients were prospectively enrolled in a case-control study. All patients had received tenecteplase (TNKtPA) together with aspirin (500 mg) and heparin (5,000 IU). Emergency angiography within 90 minutes of bolus TNK-tPA identified 13 TIMI 0–2 patients (cases) and 30 TIMI 3 patients (controls). Blood samples were collected before angiography to determine tissue factor activity associated with microparticles (TF-MP); soluble platelet glycoprotein V (sGPV) and thrombinantithrombin complexes (TAT) as markers of thrombin generation; tissue plasminogen activator (endogenous tPA+ TNKtPA), plasminogen activator inhibitor (PAI-1) and plasmin-anti-plasmin complexes (PAP) as markers of plasmin generation. The baseline characteristics of the two patients’ groups were similar with respect to sex, age, and risks factors. Cases differed from controls by higher TF-MP levels (1.9 [1–13] vs. 1 [0.6–1.3] pM), sGPV (67 [51–126] vs. (48 [39–72] ng/ml), p=0.039 and TAT (10 [4–37.5] vs. 4 [2.9–7.2] ng/ml), p=0.035. TAT correlated with TF-MP (r=0.51, p=0.0064) and sGPV (r=0.51, p=0.0018). No significant difference was observed in tPA or PAI-1 levels. PAP were lower in cases (18.83 [14.83–40.43] μg/ml) than in controls (35.83 [27.9–43.94] μg/ml), p=0.045. In conclusion, fibrinolysis failure in AMI is characterised by a higher procoagulant state associated with TF-MP and a lower plasmin generation.

Severity of venous insufficiency is related to the density of microvascular deposition of PAI-1, uPA and von Willebrand factor

VASA ◽  
2004 ◽  
Vol 33 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Kolbach ◽  
Hamulyák ◽  
Prins ◽  
Neumann ◽  
Cleutjens
Keyword(s):  
Lower Extremity ◽  
Plasminogen Activator ◽  
Von Willebrand Factor ◽  
Venous Insufficiency ◽  
Leg Ulcer ◽  
Significant Difference ◽  
Skin Biopsies ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Pai 1

Background: Impaired microcirculation in chronic venous insufficiency leads to chronic inflammation and dystrophic changes of the skin, and finally to leg ulceration. The purpose of this study was to investigate in more detail coagulation and fibrinolytic protein response of the capillaries in skin biopsies of the lower extremity. Patients and methods: From eighteen ambulant patients with venous leg ulcer(s) (n = 8) and controls (n = 10) with various degrees of venous insufficiency according to the CEAP classification, we obtained 4 mm punch biopsies. Immunohistochemical staining with tissue derived plasminogen activator (tPA), urokinase derived plasminogen activator (uPA), plasminogen activator inhibitor (PAI-1) and von Willebrand Factor (vWF) was performed and analyzed with bright field microscopy. Results: The amount of staining with vWF (p = 0.04) and uPA (p = 0.02) showed statistically significant differences, PAI-1 (p = 0.09) and tPA (p = 0.50) showed no difference between leg ulcer and control groups. A strong proliferation of capillaries with tortuous capillary loops in the papillary dermis was seen, but no statistically significant difference (M-W test, p = 0.10) was found between the groups. Comparison between CEAP classes 0–6 showed a statistically significant increased staining pattern of vWF (p = 0.06), uPA (p = 0.02) and PAI-1 (p = 0.02), but not from tPA (p = 0.30). Conclusions: In skin biopsies of the lower extremity of patients with severe venous insufficiency increased deposition of vWF, PAI-1 and uPA were found in the capillaries. These findings point to a local imbalance in coagulation and fibrinolytic status, which might contribute to impaired microcirculation and finally to the development of venous leg ulceration.

Plasminogen Activator Inhibitor 1 Is Elevated in the Children of Men with Premature Myocardial Infarction

1996 ◽  
Vol 76 (03) ◽  
pp. 417-421 ◽  
Author(s):  
Loukianos S Rallidis ◽  
Ageliki A Megalou ◽  
Nikos H Papageorgakis ◽  
Athanasios G Trikas ◽  
Grammatiki I Chatzidimitriou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Plasminogen Activator ◽  
Apolipoprotein B ◽  
Plasminogen Activator Inhibitor ◽  
Activity Levels ◽  
Plasminogen Activator Inhibitor 1 ◽  
History Of ◽  
Premature Myocardial Infarction ◽  
Young Subjects ◽  
Pai 1

SummaryTo assess whether plasminogen activator inhibitor 1 (PAI-1) activity is elevated in the progeny of young coronary men, 193 young subjects were recruited and divided into two groups. Group A consisted of 104 children whose fathers had suffered a myocardial infarction before the age of 55 (“cases”). Eighty-nine young subjects matched for age, sex, body mass index (BMI) and smoking habits without familial history of coronary artery disease (CAD) served as controls (group B). Children with a family history of diabetes mellitus or hypertension were excluded from both groups. We measured PAI-1 activity, tissue-type plasminogen activator (t-PA) antigen, a2-antiplasmin, fibrinogen, lipids and apolipoproteins in both groups. PAI-1 activity levels were also determined in the men who suffered a premature myocardial infarction 4 months after their discharge. PAI-1 activity levels were higher in cases compared to controls (3.13 ± 1.9 vs 2.17 ± 1.9 U/ml, p = 0.0014). t-PA antigen and a2-antiplasmin did not differ significantly between the two groups, while fibrinogen, total cholesterol, low-den-sity lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) were significantly higher in group A. PAI-1 was positively correlated with triglycerides (r = 0.22, p = 0.024), apolipoprotein B (r = 0.21, p = 0.039) and fibrinogen (r = 0.22, p = 0.029 ) in cases and with BMI in both cases (r = 0.37, p = 0.0003) and controls (r = 0.23, p = 0.044). In stepwise multiple regression analysis, only apolipoprotein B (p = 0.008) and BMI (p = 0.0014) were significant determinants of PAI-1 activity in cases. There was also a positive correlation between PAI-1 activity levels of the affected fathers and their children (r = 0.30, p = 0.01). The present data support the hypothesis that elevated PAI-1 levels in the offspring of men with premature myocardial infarction impair their fibrinolytic capacity contributing to their familial predisposition to CAD.

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