Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to discern biological (such as thrombotic or fibrinolytic) risk factors in patients developing restenosis after percutaneous transluminal coronary angioplasty, the following factors were measured prior to angiography in a population of 23 patients (20 men, 3 women, mean age 57 +/- 5 yr) treated by a successful angioplasty (gain > 20% and residual stenosis < 50%) for stable angina pectoris and who had a routine angiographic restudy. The following factors were thus assessed: lipid factors: cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein AI, apolipoprotein B; coagulation factors: fibrinogen, antithrombin III, fibrinopeptide A, factor VIII coagulant, factor VIII antigen, protein C; factors of physiological fibrinolysis: plasminogen, alpha 2-antiplasmin, tissue plasminogen activator and euglobulin clot lysis time before and after venous occlusion, plasminogen activator inhibitor before venous occlusion; and factors of platelet release: beta-thromboglobulin, platelet factor 4. Also studied were clinical characteristics: age, gender, diabetes, hypertension, smoking habits, previous myocardial infarction; angiographic data: global extent of coronary artery disease, location of the stenosis in a bend or branch point, complexity of the lesion, initial and residual stenosis and treatment during follow-up. The coronary angiograms were analyzed by a computer-assisted method with automatic edge detection. On angiographic criteria, 6 patients (restenosis group) were judged to have developed a restenosis (30% decrease in diameter and/or return to a 50% stenosis). The other 17 patients (those without restenosis) were considered to have a persistent success. Apart from age (group without restenosis: 55 +/- 6; restenosis group 61 +/- 5, p < 0.04), there were no differences in clinical, angiographic or treatment variables. There were no differences in lipid factors, but significant differences were observed in hemostatic variables: fibrinogen (without restenosis: 3.18 +/- 0.83; restenosis: 3.83 +/- 0.51 milligrams, p = 0.05), tissue plasminogen activator before venous occlusion (without restenosis: 10.9 +/- 26.8; restenosis: 232.5 +/- 371.2 IU, p < 0.04), euglobulin clot lysis time after venous occlusion (without restenosis: 176.5 +/- 100.5; restenosis: 78.6 +/- 40.2 min, p < 0.05) and for marker of the platelet release: platelet factor 4 (without restenosis: 10.8 +/- 7.9; restenosis: 20.5 +/- 7.5 ng/l, p < 0.04). These findings indicate that patients developing restenosis after coronary angioplasty tend to have an imbalance in the prothrombotic-antithrombotic equilibrium prior to the procedure.
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PMID:Biological risk factors for restenosis after percutaneous transluminal coronary angioplasty. 844 4

We measured plasma parameters of the prothrombotic state, namely thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA). D-dimer (DD), von Willebrand factor (vWF), tissue-type plasminogen activator (tPA), beta-thromboglobulin (beta TG), platelet factor 4 (PF4) and serotonin (5HT) in a series of 51 adult patients with chronic uremia: 22 were on maintenance hemodialysis (MHD) and 29 on conservative dietary treatment. Serum tumor necrosis factor alpha (TNF) was determined as well. Uremics presented significantly higher levels of TAT, FPA, DD, vWF, TNF, beta TG and 5HT than normal controls. Patients on conservative treatment showed lower levels of TAT, DD, TNF and beta TG than patients on MHD. Our results provide evidence that a prothrombotic state exists in chronic uremia and that MHD patients have a higher degree of hypercoagulation. Both hemodialysis procedure and uremia-related factors are likely to contribute to the hemostatic derangement.
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PMID:Plasma parameters of the prothrombotic state in chronic uremia. 844 63

The purpose of this study was to investigate the effects of beraprost sodium, a stable prostacyclin analog, on the parameters of hemostasis, fibrinolysis, and myocardial ischemia in patients with exertional angina. Thirty-one patients with exertional angina who had significant organic coronary artery stenosis in at least one of the three major coronary arteries were selected. All patients underwent quantitative exercise thallium-201 emission computed tomography before and 1 month after 120 micrograms per day of beraprost sodium administration. Before exercise, blood samples were collected from 8:30 a.m. to 9:30 a.m. after the patients had been lying in bed undisturbed for at least 10 minutes. Plasma platelet factor 4 (PF4), fibrinopeptide A (FPA), tissue plasminogen activator antigen (t-PA), and plasminogen activator inhibitor-1 activity (PAI-1) were measured. There were no significant differences in exercise parameters on both exercise tests. However, both the extent and severity scores of ischemia were significantly aggravated (p < 0.05 for both) during beraprost sodium administration. Plasma FPA levels decreased significantly during beraprost sodium administration (p < 0.01). Likewise, plasma PF4 levels decreased significantly during beraprost sodium administration (p < 0.05). As for plasma t-PA antigen levels, there was no significant difference before versus during beraprost sodium administration. Plasma PAI-1 activity levels decreased significantly during beraprost sodium administration (p < 0.05). The results indicate that beraprost sodium has strong antithrombogenic properties. However, its aggravation of myocardial ischemia may limit clinical usage.
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PMID:Effects of beraprost sodium, a new prostaglandin I2 analog, on parameters of hemostasis, fibrinolysis, and myocardial ischemia in patients with exertional angina. 854 11

To characterize the vasospastic angina patients with exercise-induced ischemia, we measured hemostasis (platelet factor 4; PF4, fibrinopeptide A; FPA) and fibrinolytic parameters (tissue plasminogen activator antigen; t-PA, free plasminogen activator inhibitor-1 antigen; free PAI-1) in 15 normal subjects and 33 vasospastic angina patients without significant coronary artery stenosis (less than 50% stenosis). All of the vasospastic angina patients began to feel chest pain within 3 months before diagnostic coronary angiography. Blood samples were obtained from all of the study patients at 8:30-9:30 am before exercise 201Tl emission computed tomography. Vasospastic angina patients were divided into 2 groups; 15 patients with exercise-induced ischemia (group 1) and 18 patients without exercise-induced ischemia (group 2). On coronary angiography, the severity of coronary artery stenosis at the site of spasm in group 1 (34 +/- 5%) was greater than that in group 2 (18 +/- 3%). Plasma FPA and PF 4 levels in group 1 were also significantly higher than those in normal subjects and group 2. Plasma t-PA and free PAI-1 levels in group 1 were significantly higher than those in normal subjects and group 2. Plasma levels of free PAI-1 group 2 were also significantly higher than those in normal subjects. The present study demonstrated that all of the patients with vasospastic angina had impaired fibrinolysis, and these patients with exercise-induced ischemia showed enhanced platelet activation, an enhanced coagulation system, and advanced atherosclerotic lesions. These results suggest that vasospastic angina with exercise-induced ischemia puts patients at increased risk for thrombus formation.
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PMID:Characteristics of vasospastic angina with exercised-induced ischemia--analysis of parameters of hemostasis and fibrinolysis. 880 21

Thirteen patients with mild hypertension (untreated diastolic blood pressure of 95 to 114 mmHg) received, in random order, three successive treatments of four weeks with placebo, spirapril (6 mg daily), or hydrochlorothiazide (HCT2) (24 mg daily). At the end of each treatment, blood samples for assessment of platelet aggregation and platelet release of platelet factor 4 (PF4) and for assessment of fibrinolysis, estimated by tissue plasminogen activator (t-PA), plasminogen activator inhibitor-type 1 (PAI-1), and euglobulin clot lysis time (ECLT), were taken, first at rest, then immediately after five to ten minutes of vigorous exercise, and finally after the subsequent hour of recovery rest. Platelet aggregation induced in vitro by adrenaline significantly decreased during treatment with HCT2, the threshold rising to 10 microM as compared with 1.0 with placebo (P < 0.05) at rest, and the threshold for adenosine diphosphate (ADP) aggregation also rose, from 2 microM to 4 (NS). The resting plasma PF4 value fell, although not significantly, during HCT2 treatment from the placebo value of 3.28 to 2.56 ng/mL. During spirapril treatment there was no change in the threshold of either adrenaline or ADP for aggregation of platelets sampled at rest, and the PF4 plasma levels showed no significant reductions at rest. However, during exercise PF4 showed an approximate doubling of the resting value irrespective of therapy. This exercise-induced increase in PF4 was significantly reduced by spirapril as compared with placebo (P < 0.05). ECLT and t-PA did not shift significantly from the placebo level during either therapy. PAI-1 did not change during spirapril therapy, but during HCT2 treatment it fell, although not significantly, to 9.36 IU/mL from 15.91 with placebo (NS). Spirapril and HCT2 did not produce any unwanted side effect on platelet function or fibrinolysis. HCT2 seems to decrease platelet activity at rest, whereas spirapril seems to some extent to decrease platelet activity at exercise.
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PMID:Effect of spirapril and hydrochlorothiazide on platelet function and euglobulin clot lysis time in patients with mild hypertension. 887 80

Basic fibroblast growth factor (bFGF) and its specific receptors have diverse roles on a variety of cell types, such as the induction of vascular smooth-muscle cell proliferation which contributes to restenosis after coronary balloon angioplasty. bFGF is also known to interact with heparan sulphate proteoglycans present on the cell surface or in the extracellular matrix. In this study, the binding of 125I-bFGF to human aortic smooth-muscle cells was investigated. 125I-bFGF binding to these cells was reversible and saturable. Scatchard analysis revealed the presence of two distinct binding sites: a high-affinity receptor (Kd=38+/-7 pM; 1480+/-220 sites/cell) and a low-affinity non-saturable binding site (Kd=8. 0+/-2.0 nM). Pretreatment of the cells with heparinase resulted in a large reduction of 125I-bFGF binding to its low-affinity receptors, suggesting that they are heparin-like molecules. The specificity of the low- and high-affinity binding sites for bFGF was determined with acidic FGF, platelet-derived growth factor-BB and epidermal growth factor, which did not compete for 125I-bFGF binding. Expression of FGF receptor isoforms analysed by reverse transcriptase-PCR revealed the presence of only the type-1 receptor. Binding to low-affinity binding sites was antagonized by heparin, suramin, protamine sulphate and platelet factor 4. Unexpectedly, these molecules also reduced the binding of 125I-bFGF to its high-affinity sites. Consistent with these results, heparin, suramin, protamine sulphate and platelet factor 4 inhibited bFGF-induced proliferation of human aortic smooth-muscle cells. Heparin abrogated bFGF-induced release of tissue-type plasminogen activator by these cells. These observations suggest that the interaction of bFGF with human aortic smooth-muscle cells is different from that described for other cells such as endothelial cells, in which heparin acts as a potentiating factor of the mitogenic activity of bFGF.
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PMID:Heparin inhibits the binding of basic fibroblast growth factor to cultured human aortic smooth-muscle cells. 930 14

Endothelial cells, circulating platelets, and proteins of the coagulation and fibrinolytic systems are known to contribute to the hemostatic processes. Various molecular markers of hemostatic alteration are found in increased amounts in the circulation during the activation of this process. In this study, we investigated serum lipoprotein (a) and plasma platelet factor 4, beta-thromboglobulin, thrombin-anthithrombin complex, fibrinopeptid A, D-dimer, tissue plasminogen activator, tissue plasminogen activator inhibitor, and fibronectin levels in patients with coronary artery disease. The levels of all these markers were found to be significantly higher as compared to the control group. Our findings suggest that patients with coronary artery disease have greater blood coagulability than controls, and the use of molecular markers has become greatly important in clinical practice.
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PMID:The molecular markers of hemostatic activation on coronary artery disease. 952 53

We review laboratory tests that evaluate thrombogenesis during acute coronary syndromes. These tests have been found to be valuable research tools in more clearly understanding the pathophysiology of acute coronary syndromes. In particular, we describe tissue factor, tissue factor pathway inhibitor, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrinopeptide A, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), t-PA-PAI complex, Bbeta 15-42-related peptides, fibrinogen degradation products, fibrin degradation products, D-dimer, platelet factor 4, beta-thromboglobulin, 5-hydroxytryptamine, thromboxane B2, prostacyclin, endothelin, angiotensin-converting enzyme, soluble thrombomodulin, C1-esterase inhibitor, anaphylotoxins C3a, C4a, and C5a, bradykinin, tumor necrosis factor, leukotriene C4, platelet activating factor, anti-phospholipid antibody, and von Willebrand factor. Some of these tests may prove to be useful in clinical diagnosis and management of acute coronary syndromes. Clinical outcome studies are needed to determine which tests may be cost effective and medically useful.
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PMID:Useful laboratory tests for studying thrombogenesis in acute cardiac syndromes. 970 94

It is generally accepted that atherosclerosis is a dynamic process in which many factors of lipid, hemostatic or other nature play their negative and positive roles. The purpose of the study was to determine the relationship between the atheromatous changes in coronary arteries being assessed angiographically and the lipid and hemostatic risk factors, as well as to select biochemical parameters, which would be helpful for prognosing the degree of intensity with regard to atheromatous changes in coronary arteries. Studies of lipid parameters and hemostasis system were performed in 31 men with atherosclerosis of coronary vessels being angiographically estimated. The degree of intensity concerning the atheromatous changes was defined in a point scale according to Gensini based on the magnitude of coronary artery stenosis and its localization in respect of significance for myocardial function. The studied patients were divided into two groups, which differed by the degree of the intensity of atheromatous changes in coronary arteries: group I--men with mild (M-CAD, score < 32) n = 15, group II--men with severe atherosclerotic changes (S-CAD, score > or = 32) n = 16. The characteristics of both groups are given in table 1. All patients were on nitrates, salicylates, beta-blockers and calcium channel blockers. No antilipemics or anticoagulants were administered. The following biochemical parameters were determined in all men: cholesterol-Ch; triglycerides-TG; phospholipids-PL; apolipoproteins: Apo A, Apo A-I, Apo B; lipoproteins: VLDL, LDL, HDL and their lipids and proteins components; lipoprotein (a)-Lp(a); fibrinogen-Fb; euglobulin lysis time-ELT; inhibitor tissue plasminogen activator PAI-1; antithrombin III--AT III; spontaneous platelet aggregation-SPA, platelet factor 4-PF 4 and glucose. Table 2 lists the lipid parameters in serum and lipoprotein fractions. The levels for apolipoproteins A, A-I, B, lipoprotein (a), hemostatic parameters and glucose are given in table 3. Tables 4 and 5 present the results of multiple regression analysis for severity of atherosclerotic changes (score--dependent variable y) lipid and hemostatic parameters and glucose (independent variables x) in both groups. Prognostic variables necessary for the best fit in the model of relationship studied have been selected. Independent variables x are listed in descending order according to the absolute value of b*x. On the basis of the performed statistical analysis of the results of studies it has been ascertained that the biochemical parameters differentiating the patients with regard to the intensity of atheromatous changes are the coefficients: LDL-Ch/HDL-Ch and Apo B/Apo A ratio, LDL-PL, Fb and ELT whose values were higher as well as HDL-Apo A-I whose value was lower in the group of men with more severe atherosclerotic changes in coronary arteries (S-CAD). The stepwise multivariate analysis indicates that the most profound prognostic significance in risk of coronary atherosclerosis is claimed successively by: glucose, LDL-PL, HDL-Apo A-I, AT III, Fb, ELT, PAI-1, SPA, Lp(a), Apo B and PF 4. The results of the accomplished studies point out that the above-mentioned lipid, hemostatic parameters and glucose may be helpful in prognosing the severity of coronary atherosclerosis.
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PMID:[Determination of the usefulness of selected biochemical parameters for assessing the advanced atheromatous changes in human coronary arteries]. 985 30

Granulocyte colony-stimulating factor (G-CSF) is used in healthy donors of peripheral blood stem cells (PBSC) for allogeneic transplantation. However, some data have recently suggested that G-CSF may induce a hypercoagulable state, prompting us to study prospectively 22 PBSC donors before and after G-CSF 5 microg/kg twice daily. We sought evidence for changes in the following parameters: platelet count, von Willebrand factor antigen (vWF:Ag) and activity (vWF activity), beta-thromboglobulin (beta-TG), platelet factor 4 (PF-4), platelet activation markers (GMP-140 and PAC-1), activated partial thromboplastin time (aPTT), prothrombin time (PT), coagulant factor VIII (FVIII:C), thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2), thrombomodulin (TM) and tissue plasminogen activator antigen (tPA:Ag) prior to G-CSF and immediately before leukapheresis. ADP-induced platelet aggregation studies were also performed. G-CSF administration produced only mild discomfort. We found a significant increase in vWF:Ag (from 0.99 +/- 0.32 U/ml to 1.83 +/- 0.69 U/ml; P < 0.001), in vWF activity (from 1.04 +/- 0.34 U/ml to 1.78 +/- 0.50 U/ml; P < 0.001) and in FVIII:C (from 1.12 +/- 0.37 U/ml to 1.73 +/- 0.57 U/ml; P < 0.001) after G-CSF. Of note, four donors with low baseline vWF had a two- to three-fold increase after receiving G-CSF. G-CSF had no impact on the platelet count, beta-TG, PF-4, GMP-140 or PAC-1. The final% of platelet aggregation decreased from 73 +/- 22% to 37 +/- 26% after G-CSF (P < 0.001). We found a significant decrease in aPTT after G-CSF (29.9 +/- 3.1 s to 28.3 +/- 3.3 s; P = 0.004), but the PT was unaffected. In addition, we also observed a significant increase in TAT, F1+2 and TM, but not in tPA:Ag. Our data suggest that G-CSF may possibly induce a hypercoagulable state by increasing levels of FVIII:C and thrombin generation. In contrast to this information, we found reduced platelet aggregation after G-CSF administration. The clinical implications of these findings remain unclear and larger studies are definitely required.
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PMID:A prospective study of G-CSF effects on hemostasis in allogeneic blood stem cell donors. 1037 63


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