Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the effect of purified immunoglobulin G (IgG) on endothelial cell functions in 16 patients with lupus anticoagulant, 9 of whom had systemic lupus erythematosus (SLE). Spontaneous or thrombin-stimulated secretion of prostacyclin (PGI2) by cultured human endothelial cells from umbilical cord vein (HUVEC) was not inhibited by the patient's IgG. Nor was spontaneous release of tissue plasminogen activator (t-PA) or of its inhibitor (PAI) modified in the presence of patient's IgG. The rate of activation of purified protein C (PC) by HUVEC in the presence of thrombin was significantly lowered by patient's IgG or Fab' fragment (inhibition of 43%). Neutralization of this effect was obtained by incubation of a greater quantity of phospholipids (phosphatidylcholine, phosphatidylserine) with the patient's IgG. Activation of PC was also performed using purified rabbit thrombomodulin (TM) and a similar inhibition of the patient IgG was observed (inhibition of 48%) but the activation of Gla-domainless PC was not modified.
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PMID:Effect of lupus anticoagulant on antithrombogenic properties of endothelial cells--inhibition of thrombomodulin-dependent protein C activation. 284 52

We have previously demonstrated that plasminogen activator inhibitor (PAI-1) is associated with the extracellular matrix of cultured bovine smooth muscle cells (Knudsen, B.S., Harpel, P.C., Nachman, R.L. (1987) J. Clin. Invest. 80, 1082-1089). In this report we describe the physiologic role of PAI-1 during the interaction of the tissue plasminogen activator (t-PA) secreting Bowes human melanoma cell line with endothelial extracellular matrices. In addition we have characterized the t-PA.PAI complexes formed during this interaction in the presence and absence of plasminogen. In the absence of plasminogen, a 104-kDa complex between Bowes t-PA and PAI-1 appears in the supernatant. In the presence of plasminogen, PAI initially prevents plasmin formation on the matrix and protects the matrix from degradation by plasmin. The 104-kDa t-PA.PAI complex is degraded into a 68 and a 47-kDa complex by small amounts of plasmin generated from secreted Bowes t-PA and plasminogen. Analysis of these complexes revealed that t-PA is rapidly cleaved by plasmin within the complex whereas complexed PAI-1 is not further degraded. Matrix-associated PAI-1 may play an important role in the protection of extracellular matrices from remodeling and degradation by cellular t-PA and plasminogen.
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PMID:Matrix plasminogen activator inhibitor. Modulation of the extracellular proteolytic environment. 296 24

Using affinity chromatography on lysine Sepharose 4B, a fast-acting tissue plasminogen activator inhibitor (t-PAI) was partially purified from t-PAI-rich plasma from patients with recurrent DVT. Its inhibition of tissue plasminogen activator (t-PA) was demonstrated in functional assays and its reaction with 125I-t-PA was analyzed by autoradiography following SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis). When the t-PAI was mixed with an equimolar concentration of t-PA at 37 degrees C, the half-life of free one-chain and two-chain 125I-t-PA was 1.8 and 0.8 min, respectively. The rate of complex formation between 125I-t-PA and t-PAI was similar both in patient plasma, pregnancy plasma and platelet lysates made from platelet-rich normal, patient and pregnancy plasma. The molecular weights of the complexes between t-PA and the inhibitors in patient plasma and in the different platelet lysates were identical, while that of the inhibitor complex formed in pregnancy plasma was found slightly higher by SDS-PAGE indicating that the pregnancy plasma t-PAI differs from the fast-acting t-PAI found in plasma from thrombotic patients and in platelet lysates.
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PMID:Plasminogen activator inhibitors in plasma and platelets from patients with recurrent venous thrombosis and pregnant women. 308 15

Myocardial infarction is frequently caused by acute coronary thrombosis. A previous study in patients three years after myocardial infarction has shown twice as high concentrations of the rapid inhibitor of plasminogen activator (t-PAI) as in healthy controls. The present study involves 29 patients with acute onset of myocardial infarction. Already on admission the mean concentration of t-PAI was 16.5 +/- 7.4 units/ml as compared to 7.5 +/- 2.3 in healthy controls. It is presently unknown if moderately elevated t-PAI levels contribute to a delay of the spontaneous thrombolysis of the coronary occlusion, thus promoting the development of myocardial infarction.
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PMID:Elevated levels of the rapid inhibitor of plasminogen activator (t-PAI) in acute myocardial infarction. 311 11

The site of the reaction between plasminogen activators and plasminogen activator inhibitor 1 (PAI-1) was investigated in cultures of human umbilical vein endothelial cells. In conditioned medium from endothelial cells, two forms of a plasminogen activator-specific inhibitor can be demonstrated: an active form that readily binds to and inhibits plasminogen activators and an immunologically related quiescent form which has no anti-activator activity but which can be activated by denaturation. In conditioned medium, only a few percent of PAI-1 is the active form. However, the addition of increasing concentrations of tissue-type plasminogen activator (t-PA) or urokinase to confluent endothelial cells produced a saturable (3.0 pmol/5 x 10(5) cells), dose-dependent increase of the activator-PAI-1 complex in the conditioned medium even in the presence of actinomycin D or cycloheximide. This resulted also in a dose-dependent decrease of the residual PAI activity measured by reverse fibrin autography both in the conditioned medium and cell extracts. Short-time exposure of endothelial cells to a large amount of t-PA caused almost complete depletion of all cell-associated PAI activity. Although there was no detectable PAI activity even after activation of PAI by denaturants or antigen in the culture medium at 4 degrees C without the addition of t-PA, the addition of t-PA at 4 degrees C not only resulted in the formation of 70% of the amount of the t-PA.PAI complex in conditioned medium at 37 degrees C, but also induced PAI-1 antigen in a time and dose-dependent manner in the conditioned medium. Moreover, 125I-labeled t-PA immobilized on Sepharose added directly to endothelial cells formed a complex with PAI-1 in a dose-dependent manner. On the other hand, no detectable complex was formed with PAI-1 when Sepharose-immobilized 125I-labeled t-PA was added to endothelial cells under conditions in which the added t-PA could not contact the cells directly but other proteins could pass freely by the use of a Transwell. All these results suggest that a "storage pool" on the surface of endothelial cells or the extracellular matrix produced by endothelial cells contains almost all the active PAI-1, and reaction between PA and PAI-1 mainly occurs on the endothelial cell membranes, resulting in a decrease of the conversion of active PAI-1 to the quiescent form.
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PMID:Interaction of tissue-type plasminogen activator and plasminogen activator inhibitor 1 on the surface of endothelial cells. 312 83

Vascular or tissue-type plasminogen activator (plasma t-PA) is the circulating physiological fibrinolytic enzyme of endothelial cell origin which function is regulated by fibrin and a specific inhibitor (PAI). To study the pattern of release of t-PA and the behavior of t-PA-PAI complexes in plasma we determined t-PA activity in 44 healthy subjects before and after 10 min of forearm venous occlusion using a new spectrophotometric solid-phase fibrin-tPA activity assay. The assay is based on 1) the high affinity binding of t-PA to fibrin, and 2) the detection of fibrin-bound t-PA by measuring the release of pNA from a chromogenic substrate in the presence of plasminogen. Values at rest were rather undetectable in plasma (0.05 +/- 0.03 IU/ml, in 23 out of 44 samples) but were positively detected in all the euglobulins: 0.88 +/- 0.68 IU/ml. After venous occlusion the majority of plasmas (36 out of 44) showed a slight increase in t-PA activity (0.65 +/- 0.63 IU/ml) as compared to the important level observed in all the euglobulins (9.78 +/- 9.58 IU/ml). So, the ratio plasma/euglobulin t-PA activity was very low (0.06) and remained identical in both pre- and postocclusion samples. However, when diluted plasmas were tested the inhibitory effect disappeared and t-PA activity increased indicating that although t-PA circulates in a neutralized state it can be available for fibrinolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release pattern of the vascular plasminogen activator and its inhibitor in human postvenous occlusion plasma as assessed by a spectrophotometric solid-phase fibrin-tPA activity assay. 312 85

The effects of sulfonylureas on the production of plasminogen activator (PA) and antiactivator (PAI) were investigated using bovine aortic endothelial cells. All compounds studied stimulated PA release (1.3- to 5.2-fold), with glipizide being the most potent, followed by tolazamide, chlorpropamide, and tolbutamide, in that order, while glyburide was the least effective. Both tissue-type and urokinase-type PA production was enhanced. Studies using metabolic inhibitors indicated that both RNA and protein syntheses are required for the sulfonylurea-mediated stimulation of PA release. In addition to continuous release of the two PAs, there was also a continuous release of a single PAI, which did not show an increase after the sulfonylureas. These results suggest that, in addition to their beneficial effects in the treatment of diabetes mellitus, some sulfonylurea compounds may also have significant thrombolytic effects. These results also suggest that pharmacological enhancement of PA production by vascular endothelial cells may be a promising antithrombotic mechanism.
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PMID:Effects of sulfonylureas on the synthesis and secretion of plasminogen activator from bovine aortic endothelial cells. 312 27

During a survey of four month's duration the following parameters were determined in 43 healthy blood donors (22 males, 21 females; mean age 29 years/20-49/): plasminogen activity, plasminogen concentration, alpha 2-antiplasmin (alpha 2-AP) activity, alpha 2-AP concentration, tissue type plasminogen activator (t-PA) activity, t-PA concentration, plasminogen activator inhibitor--I (PAI-I) activity, AT III activity, AT III concentration and heparin cofactor II (HC II) activity. Normal values including standard deviation (x +/- 2s) were: plasminogen activity: 96.3% (65.9-126.8), plasminogen concentration: 12.2 mg/dl (7.7-16.8), alpha 2-AP activity: 99.9% (83.8-116), alpha 2-AP concentration: 108.1% (84.5-131.8), t-PA activity: 0.85 IU/l (0.0-1.92), t-PA concentration: 10.3 ng/ml (2.5-18.1), PAI-I activity: 15.2 AU/ml, AT III activity: 111.4% (87.8-134.9), AT III concentration: 31.6 mg/dl (24.2-39.1) and HC II activity: 110.7% (81.4-140.0). Concerning plasminogen values no sex related difference could be stated. Women who were smokers and used oral contraceptives tended to present elevated t-PA activity levels due to a lower activity of PAI-I, although this tendency was not significant. Determining concentration and activity of components in the fibrinolytic system plays an important part in the diagnosis, therapy and prognosis of thrombophilic disorders.
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PMID:Reference values and variability of plasminogen in healthy blood donors and its relation to parameters of the fibrinolytic system. 312 9

Based on animal data it has been hypothesised that lungs may regulate systemic fibrinolysis. To test this hypothesis 12 patients undergoing infrarenal aortic reconstruction due to arteriosclerotic disease were evaluated for influence of the respiratory pattern on release of tissue plasminogen activator (t-PA) and its inhibitor (PAI) in systemic and pulmonary arterial blood. Blood samples were drawn simultaneously from the pulmonary artery and a radial artery at defined times before and during surgery. Samples were also collected during application of positive end expiratory pressure (PEEP) of 5, 10 and 15 cmH2O. The blood samples were analysed for euglobulin clot lysis time (ECLT), t-PA activity, t-PA antigen and PAI. ECLT was not altered during surgery and t-PA activity was below the detectable limit. Before surgery t-PA antigen was 14.5 +/- 1.3 ng/ml and PAI 15.1 +/- 2.8 U/ml (mean +/- SEM). PAI was significantly elevated at end of surgery. There were no differences between samples from systemic and pulmonary arteries. Following application of 5, 10 and 15 cmH2O PEEP the fibrinolytic parameters were unchanged. Thus, in the present study on arteriosclerotic patients undergoing abdominal aortic reconstructions no influence from the respiratory pattern on systemic fibrinolysis could be demonstrated.
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PMID:Tissue plasminogen activator and its inhibitor following major surgery in relation to ventilatory pattern. 312 33

Fibrinolysis dependent on the release of tissue plasminogen activator (t-PA) can only be explored after stimulation eliciting the release of t-PA from endothelial cells. The choice of the stimulus and test assay is of utmost importance in discriminating patients at risk for persistent thrombosis and in identifying acquired or genetic abnormalities of t-PA synthesis or release from endothelial cells in pathologic conditions. The present study was designed to compare the efficacy and reproducibility of the fibrinolytic response to desmopressin acetate (deamino-8-D-argininevasopressin) (DDAVP) by use of various routes of administration with the response to the venous occlusion test. Nine healthy male volunteers were randomly administered intravenous desmopressin acetate, intranasal drops and intranasal spray. The results from tests of euglobulin lysis time, t-PA activity, t-PA antigen levels, and t-PA fast-acting inhibitor (plasminogen activator inhibitor [PAI]) level were compared with those obtained after venous occlusion. The only test that elicited the release of free t-PA activity in the circulation in all volunteers was the intravenous administration of 0.4 microgram/kg desmopressin acetate, and the most reliable test assay was t-PA activity measured in the euglobulin fraction of plasma. Intravenous desmopressin acetate induced the release of large amounts of t-PA in most cases and caused a significant fall in PAI. Other routes of administration of desmopressin acetate, along with venous occlusion, identified many nonresponders who proved to be false negative. The relevance of these data was demonstrated in a study in nine patients with thromboembolic phenomenon or related disorders.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A dynamic test to investigate potential tissue plasminogen activator activity. Comparison of deamino-8-D-argininevasopressin with venous occlusion in normal subjects and patients. 313 70


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