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)

The purpose of this study was to compare vascular damage and thrombus formation in the coronary and femoral arteries after balloon angioplasty, and to develop a physiological animal model of intracoronary occlusive thrombus using the balloon angioplasty technique. Angioplasty of the left anterior descending coronary arteries of 14 dogs was performed with an oversized balloon catheter at a high inflation pressure (150 PSI). This was followed angiographically (PTCA protocol). Dogs that showed arterial occlusion were divided into 2 groups. The dogs in 1 group were killed with an overdose of sodium pentobarbital, and those in the other group were infused with a tissue-type plasminogen activator (t-PA; 300,000 unit/kg). Angioplasty of the femoral and profunda femoris arteries (n = 5) was performed in 5 other dogs (PTA protocol). All of the animals were eventually sacrificed and tissue preparations were made from all 3 types of arteries. In the PTCA protocol, acute arterial occlusion was seen angiographically within 2 h in 10 of the 14 dogs. A histological study of the acutely occluded arteries (n = 5) showed thrombotic occlusion and severe arterial damage with medial tearing. T-PA was infused to 5 of the dogs with acute occlusion, and all showed reperfusion. A histological study of these animals showed severe arterial damage, but no macroscopic thrombus. In 4 dogs without acute occlusion, none of the 10 arteries examined were acutely occluded. In the PTA protocol, none of the 10 arteries were acutely occluded. A histological study showed fewer thrombi and less severe arterial damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An animal model of coronary thrombosis and thrombolysis--comparisons of vascular damage and thrombus formation in the coronary and femoral arteries after balloon angioplasty. 823 Jun 71

Blood glucose, cholesterol and triglyceride levels were determined and the venous occlusion test (VOT) was administered to 15 vegetarians (mean age 46.2 years, SD 15.1) and 20 non-vegetarians (mean age 38.3 years, SD 8.3). The tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI) and euglobulin lysis time (ELT) were measured before and after VOT. The means of all the parameters were not significantly different between vegetarians and non-vegetarians. TPA increased after VOT in both the vegetarians and the non-vegetarians, but the changing amplitudes of tPA, PAI and ELT induced by VOT were not significantly different in either group. This study evidenced no significant difference in the changes of fibrinolytic activity between vegetarians and non-vegetarians.
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PMID:Influence of vegetarianism on fibrinolytic activity. 823 42

Thrombolytic therapy has been proposed in the treatment of cerebrovascular occlusive disease. Early clinical experiences with Urokinase and Streptokinase raised concern about the risk of hemorrhagic complications. More recently, tissue plasminogen activator (tPA) has been evaluated experimentally with promising results. Its clinical utilization has been recently initiated. A review of experimental and clinical data on thrombolysis in cerebral ischemia is presented. TPA treatment produced recanalization and clinical improvement in several patients. The rate of intracranial hemorrhagic complications is similar to the incidence of spontaneous hemorrhagic conversion of ischemic infarction. Nevertheless, large placebo-controlled clinical trials are necessary to further define the efficacy and the optimal modality of administration of tPA in thromboembolic stroke.
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PMID:Thrombolysis in cerebral ischemia. A review of clinical and experimental data. 830 72

Triaging patients suspected of myocardial infarction is performed primarily in the coronary care unit, with infarction determined within 12 to 24 hours, and only about 20% are subsequently shown to have myocardial infarction. Plasma MB CK is not elevated until 8 to 10 hours after onset, and the ECG is unreliable; thus, the need has arisen for a new "diagnostic mind-set." The need is threefold: (1) more effective triaging in the emergency room to prevent unnecessary use of hospital beds, particularly those in the intensive care units, (2) to administer thrombolytic therapy in the early hours, and (3) earlier detection of coronary reocclusion and reinfarction. Diagnostic imaging techniques such as pyrophosphate, thallium-201 technetium sestamibi, or positron emitting agents lack the necessary early diagnostic specificity, but echocardiography has potential although its specificity is limited. Plasma CK isoforms provide diagnostic sensitivity and specificity of 96% and 94%, respectively, within the initial 4 to 6 hours of onset and can be assayed within minutes. In a prospective study of 1100 patients suspected of infarction, with conventional MB CK, 22% of the patients admitted to the coronary care unit would have had infarction, whereas using the CK isoforms, 75% had infarction and about 50% were discharged home. A scenario for the future might be to initiate thrombolytic therapy outside the hospital (eg, recombinant tissue-type plasminogen activator [r-TPA] 20 mg bolus) and upon arrival, confirm or exclude infarction by the MB CK isoform which can be performed in the emergency room in 20 minutes to determine whether thrombolytic therapy and heparin should be continued.
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PMID:Earlier diagnosis and treatment of acute myocardial infarction necessitates the need for a 'new diagnostic mind-set'. 795 25

We studied the interaction of two thrombolytic agents, recombinant-tissue plasminogen activator (r-TPA) and low molecular weight urokinase (UK), with platelet aggregation in the absence or presence of unfractionated heparin (UH). With platelet rich plasma (PRP), a dose dependent inhibition was seen for both r-TPA and UK. However, this effect was more evident in the presence of r-TPA. UH did not modify this effect. However, it enhanced platelet aggregation induced by ADP and decreased the aggregation induced by collagen (COL) as already shown by us. With washed platelets, only r-TPA decreased platelet aggregation in a dose dependent manner in the presence of COL and only at the highest dose (100 micrograms) in the presence of TH. The presence of ten units of plasminogen (PLG) together with 10 micrograms of r-TPA or 1250 units of UK totally inhibited TH-induced platelet aggregation. UH reversed this effect. In contrast, when COL was the aggregating agent, the inhibition of platelet aggregation in presence of PLG, seems to be further increased by UH. Since UH is an adjunct of thrombolytic therapy to prevent rethrombosis, this double edged sword could partially explain the lack of therapeutic effect in some patients.
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PMID:Effect of recombinant-tissue plasminogen activator, low molecular weight urokinase and unfractionated heparin on platelet aggregation. 840 76

Elevated levels of lipoprotein(a) [Lp(a)] were shown to be an independent cardiovascular risk factor. Structural homologies between Lp(a) and plasminogen could be of importance for this. In the present study, the influence of Lp(a) on in vitro lysis of thrombi produced in recalcified whole blood was investigated. Of 120 healthy volunteers, 21 (18%) had serum Lp(a) levels > or = 25 mg/dl (median 70 mg/dl). Compared to 46 controls with serum Lp(a) < 25 mg/dl (median 7 mg/dl), the weight of whole blood thrombi generated in vitro was similar (96 +/- 11 vs. 94 +/- 13 mg). Thrombolysis with exogenously added tissue plasminogen activator (TPA; 0.1, 0.4 and 1.6 mg/l) was not affected by the ex vivo concentration of Lp(a). In persons with elevated Lp(a), plasma TPA levels were higher than in persons with low Lp(a) [15.7 +/- 1.5 vs. 11.7 +/- 1.2 micrograms/l; p = 0.051], but plasminogen activator inhibitor (PAI) activity and the plasma concentrations of PAI-1 were also higher. When Lp(a) was added in vitro to blood with low baseline Lp(a) [median final concentration 47 mg/dl], thrombolysis was significantly inhibited with low doses of TPA (0.1 and 0.4 mg/l), but remained unaffected with TPA 1.6 mg/l. Thus, the inhibitory effect of Lp(a) on thrombolysis seems to be counterregulated in blood of healthy volunteers with elevated Lp(a).
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PMID:Effects of lipoprotein(a) on in vitro lysis of whole blood thrombi from healthy volunteers. 849 62

Collagen plays a specific role in the maintenance of vascular integrity and in the thrombosis and scar formation processes. Therefore we found it interesting to study the changes in interstitial collagen metabolism during acute myocardial infarction treated with thrombolytic agents. Changes in collagen synthesis were evaluated by obtaining assays of the serum concentrations of the carboxyterminal propeptide of type I procollagen. Except fibrin plasmin is capable of degrading extracellular matrix components including collagen, and this capability was evaluated by monitoring the serum concentrations of the aminoterminal propeptide of type III procollagen. Twenty-four patients with suspected acute myocardial infarction and indications for thrombolytic therapy were randomized to receive either streptokinase (n = 11) or tissue plasminogen activator (n = 13). The patient groups were identical in their clinical characteristics. Serum levels of the aminoterminal propeptide of type III collagen increased rapidly on infusion of the thrombolytic agents, with the maximal mean increases of 44% and 16% in the streptokinase and TPA-treated groups, respectively. Levels of the carboxyterminal propeptide of type I collagen did not change during the thrombolytic therapy. A transient decrease occurred in the type I propeptide concentration at postinfarction day 2, and this decrease was followed by a secondary increase at days 4 to 6 in both patient groups studied. We conclude that thrombolytic agents stimulate the breakdown of interstitial collagen and that the collagen-degrading activity of TPA is lower than that of streptokinase. This factor may contribute to the relatively higher rethrombosis rate seen after TPA, because exposed collagen in the affected vascular wall stimulates thrombosis formation. On the other hand, increased collagen degradation followed by inhibition of collagen synthesis in the infarcted myocardium might increase the risk for cardiac rupture, especially after streptokinase treatment.
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PMID:Changes in interstitial collagen metabolism during acute myocardial infarction treated with streptokinase or tissue plasminogen activator. 855 22

This study assessed the short- and long-term effects of an energy-restrictive diet with or without exercise on plasminogen activator inhibitor-1 antigen (PAI-1 Ag) and PAI-1 activity, tissue-type plasminogen activator antigen (TPA Ag), and fibrinogen serum levels. Healthy, overweight postmenopausal women (age, 53.8+/-2.5 years; body mass index, 25 to 42 kg/m2; n=121) were randomly assigned to one of three groups: control, 4200-kJ/d diet, or 4200-kJ/d diet with combined aerobic and anaerobic exercise. PAI-1 activity and PAI-1 Ag, TPA Ag, and fibrinogen levels were measured at baseline, after a 12-week intervention, and after a further 6-month follow-up. PAI-1 Ag and activity and TPA Ag were positively correlated with serum triglyceride levels, the abdominal-to-total-body fat ratio (as assessed by total-body dual-energy x-ray absorptiometry), fasting blood glucose, and systolic BP and negatively with HDL cholesterol and sex hormone-binding globulin. The diet led to profound decreases and normalization of PAI-1 activity (approximately 50%), PAI-1 Ag (approximately 30%) and TPA Ag (approximately (29%), but exercise conferred no additional effect. Fibrinogen did not change. At follow-up there were no longer any significant changes (P>.05). In conclusion, PAI-1 Ag and activity as well as TPA Ag seem to be part of the metabolic syndrome X. The diet made the blood less thrombogenic in the short term with no effect of the added exercise.
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PMID:Plasminogen activator inhibitor-1, tissue-type plasminogen activator, and fibrinogen: Effect of dieting with or without exercise in overweight postmenopausal women. 863 Jun 63

Mortality rates associated with cardiovascular disease (CVD) are high in long-term dialysis patients. Increased levels of plasma fibrinogen (FBG), coagulation factor VII (FVII), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) as well as hyperlipidemia are regarded as important risk factors for CVD. To investigate whether there are differences in the risk of CVD between chronic hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients, serum lipid levels and plasma FBG, FVII, t-PA, and PAI-1 levels were measured in 17 patients on HD and 17 patients on CAPD. FBG was measured by the thrombin time method, FVII activity (FVIIc) by the chromogenic prothrombin time method, and t-PA and PAI-1 activity by the chromogenic substrate assay. No difference was found in body mass index (BMI) between HD and CAPD patients. Total cholesterol (TC), TC/high-density lipoprotein (HDL)-C ratio, low-density lipoprotein (LDL)-C, and triglycerides (TG) were significantly increased, and HDL-C was significantly decreased in CAPD patients compared with HD patients. FBG and FVIIc were significantly elevated in CAPD patients compared with controls or HD patients. T-PA activities were significantly higher in HD and CAPD patients than in controls. CAPD patients showed significantly higher PAI-1 activities than controls or HD patients. Significant positive correlations were found between FBG or FVIIc and TC, between FBG and LDL-C or TG, and between FVIIc and LDL-C in these patients. T-PA showed significant negative correlations with FBG, PAI-1, TC, LDL-C, and TG. There was a significant positive correlation between PAI-1 and TG and a significant negative correlation between PAI-1 and HDL-C. We conclude that CAPD patients may have a greater risk of CVD than do HD patients, and that coagulation and fibrinolytic activity are correlated with lipid disorders in these patients.
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PMID:Fibrinogen, coagulation factor VII, tissue plasminogen activator, plasminogen activator inhibitor-1, and lipid as cardiovascular risk factors in chronic hemodialysis and continuous ambulatory peritoneal dialysis patients. 865 Dec 50

Treatment of rat C6 glioma with high doses of 13 cis-retinoic acid (cRA) was responsible for death related to haemorrhagic necrosis localized to the tumor. Our aim was to explore this adverse effect of retinoid treatment. We show that cRA-treated C6 glioma at 25 mg/kg/day for 18 days exhibits in vivo an increase T-PA activity, which is responsible for a localized tumor fibrinolytic activity. Production of t-PA is supported by specific enhancement of gene expression, as was shown by the increase in t-PA mRNA (x 2.3). This production is a direct effect of cRA when treating the tumor, since tumor cells themselves do not produce enough t-PA and treatment of control rats does not increase the t-PA level. T-PA production by rat C6 glioma is in vivo related to the specific synthesis of t-PA by the C6 cell-line. The stimulation of C6 cell-line by cRA in vitro is dose-dependent and reached a maximum for 3 and 30 microM at the 72nd h. So cRA-treated C6 glioma cells produce t-PA which appears to be the major species associated with the fibrinolytic activity-induced intra-tumoral haemorrhage after exposure to retinoid treatment.
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PMID:Retinoids induced t-PA synthesis by C6 glioma cells--role in tumoral haemorrhagic necrosis. 881 86


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