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

Procoagulant, anticoagulant, and fibrinolytic activities are associated with endothelial cells and involve the production, secretion, and receptor mediated binding of proteins involved in these processes. The procoagulant aspect of endothelial cells function involves the production and release of von Willebrand Factor(vWF), the production of tissue factor, and the presence of Factor IX/IXa receptors on the cell surface. Secretion of vWf will promote the initial steps in thrombus formation by supporting platelet-platelet interaction and platelet-subendothelial matrix adhesion. Tissue factor which is undetectable in resting cells appears after exposure to various cytokines and initiates factor VIIa activation of factors IX and X. Receptors of Factor IX/IXa are also present and mediate the assembly of the prothrombinase complex on the endothelial cell surface. The anticoagulant pathway involves the cell surface protein thrombomodulin, protein C and its cofactor protein S. Thrombomodulin binds thrombin which activates protein C which in the presence of protein S cleaves and inactivates Factors V and VIII. Inactivation of these two coagulation cofactors halts the coagulation. Finally, endothelial cells also play a pivotal role in the fibrinolytic system. Production and regulated secretion of tissue plasminogen activator creates a profibrinolytic state in the endothelial cell environment. In addition, receptors for plasminogen and urokinase are also present, constituting a cell surface mediated fibrinolytic pathway. Plasminogen activator inhibitor type I, the primary inhibitor of tPA, is also produced by endothelial cells. Thus endothelial cells can promote and inhibit fibrinolysis, depending on the prevailing environmental conditions.
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PMID:[Endothelial cells and vascular hemostasis]. 131 12

Plasma concentrations of endothelium-associated proteins (EAP) (plasma fibronectin (PFN), angiotensin-converting enzyme, factor VIII-related antigen (F VIII-R:Ag)) and tissue plasminogen activator and serum thyroid hormone concentrations were studied in nine patients with anorexia nervosa (AN), before and after weight gain. Before weight gain (-35.9 (SE 2.3)% of standard body-weight) PFN was significantly reduced and F VIII-R:Ag was significantly increased in AN patients compared with the concentrations in control subjects (211.5 (SE 14.9) v. 274.7 (SE 16.6) micrograms/ml, P < 0.05; 129.2 (SE 14.1) v. 88.2 (SE 9.7) %, P < 0.05 respectively). Serum triiodothyronine (T3) and free T3 levels were also significantly lower before weight gain in AN patients (0.85 (SE 0.07) v. 1.53 (SE 0.08) nmol/l, P < 0.001; 2.57 (SE 0.23) v. 5.31 (SE 0.34) pmol/l, P < 0.001 respectively), although serum thyroxine (T4), free T4, and thyrotropin concentrations were within the normal range throughout the study periods. Following weight gain, PFN and F VIII-R:Ag concentrations normalized as did the thyroid hormone levels. The incremental changes in PFN levels correlated significantly with those in serum thyroid hormone concentrations (T3, r 0.79, P < 0.01; free T3, r 0.84, P < 0.01). These findings suggest that PFN levels may be directly related to serum T3 concentrations in AN patients.
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PMID:Alterations in endothelium-associated proteins and serum thyroid hormone concentrations in anorexia nervosa. 132 1

Severe bleeding resulting from excessive fibrinolysis has been observed in patients with primary amyloidosis. The authors studied a patient with this hemostatic disorder before and during therapy with epsilon-aminocaproic acid. Excessive fibrinolysis was associated with depressed plasma concentrations of coagulation Factors XII, XI, high-molecular-weight kininogen, and Factors VIII and V; and plasminogen and alpha-2-plasmin inhibitor. These deficiencies were corrected with treatment. The functional and antigenic concentrations of tissue plasminogen activator and plasminogen activator inhibitor in the patient's plasma were normal. Urokinase-type activator activity and antigen were three to five times elevated in the patient's plasma. Results of immunoprecipitation showed that single-chain urokinase-type activator was the primary urokinase-type activator species in the patient's plasma. Excessive fibrinolysis in patients with amyloidosis results from increased plasma single-chain urokinase-type activator activity.
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PMID:Excessive fibrinolysis in amyloidosis associated with elevated plasma single-chain urokinase. 148 7

The t-PA/PAI-1 complex is a good indicator of the release of fibrinolysis activators and inhibitors from the vascular wall, but its clinical significance in chronic ischemic heart disease is unclear. The plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and the t-PA/PAI-1 complex (including various coagulation factors) were assayed in 72 patients with coronary artery disease (CAD) and 29 control (C) subjects. The CAD patients were subdivided into 3 groups: single-vessel disease (G1, n = 30), double-vessel disease (G2, n = 20), and triple-vessel disease (G3, n = 22). The patients with triple-vessel disease had higher fibrinogen values (G3: 318 +/- 75 mg/dl, C: 263 +/- 56), factor VII activity (G3: 143 +/- 36%, C: 123 +/- 14), and t-PA antigen levels (G3: 4.7 +/- 0.8 ng/ml, C: 3.3 +/- 0.7) than controls. Patients with double- and triple-vessel disease also showed higher levels of factor VIII, vWF antigen, thrombin-antithrombin III complex (G1: 2.3 +/- 0.6 ng/ml, G2: 2.7 +/- 0.5, G3: 3.1 +/- 0.5, C: 2.0 +/- 0.5), and t-PA/PAI-1 complex (G1: 13.9 +/- 6.1 ng/ml, G2: 16.4 +/- 4.6, G3: 18.2 +/- 5.9, C: 10.7 +/- 4.9) than control subjects. The t-PA/PAI-1 complex levels were correlated significantly with the activities of factors VII and VIII and the thrombin-antithrombin III complex. These findings suggest that patients with CAD have greater blood coagulability than controls, and that this difference is related to the severity of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma t-PA/PAI-1 complex and blood coagulability in patients with coronary artery disease. 152 91

The effects of physical training on hemostatic parameters were evaluated in 56 postmyocardial infarction (MI) patients before and after one month of systematic physical training and in 30 control post-MI patients, who did not undergo such training. There were no significant changes in prothrombin time (PT) and alpha 1-antitrypsin (alpha 1AT) at the beginning and end of the study in either group. Levels of fibrinogen, Factor VIII: C (VIII:C) and von Wildebrand antigen (vWf:Ag), and activities of ATIII and plasminogen (Plg) were significantly decreased in the group with physical training (p less than 0.05), while values were unchanged in the control group. Hematocrit, platelet counts, and alpha 2-plasmin inhibitor (alpha 2PI) activities also decreased in the physical training group (p less than 0.05). In contrast, these variables increased in the control group (p less than 0.05). Activated partial thromboplastin time (aPTT) tended to be prolonged in the group with physical training, while it was shortened in the control group. In a subset of 20 patients with physical training, resting levels of plasmin-alpha 2PI complex (PIC), thrombin-antithrombin III complex (TAT), protein-C (P-C:Ag), plasminogen activator inhibitor-1 (PAI-1), VII:C, and P-C activities had significantly decreased after one month of physical training (p less than 0.05), although tissue plasminogen activator activities remained unchanged. Physical training appeared to suppress coagulability as indicated by the decrease in fibrinogen, VIII:C, vWf:Ag, VII:C, and TAT, and prolongation of aPTT. The decrease in plasminogen, t-PA:Ag, alpha 2PI, PAI-1, and PIC after physical training may result from the decreased coagulability. In conclusion, physical training appears to induce a suppression of the coagulation system in patients in the recovery phase of MI.
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PMID:Blood coagulability and fibrinolytic activity before and after physical training during the recovery phase of acute myocardial infarction. 162 56

16 coagulant and 7 fibrinolytic parameters were determined in 121 normal subjects and 456 patients with various types of viral hepatitis. The results showed that plasma concentration of F VIII: c, vWF: Ag and vWF: Ag/VIII: c (P less than 0.01) were much higher than those in the controls. Plasma level of other coagulant factors was progressively reduced when the severity of hepatitis was decreased. The changes of fibrinolytic activity suggest that t-PA, PL and FDP were increased, while PAI, PLG, and alpha-PI were decreased. The results of this study may provide an experimental basis for further study of hemorrhage mechanism and prognosis in patients with viral hepatitis.
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PMID:[Changes in plasma coagulant factors and plasma fibrinolytic activity in patients with viral hepatitis]. 166 71

The effects of desmopressin and dextran on haemostasis and fibrinolysis were studied in four healthy volunteers. Both drugs were compared to placebo, each volunteer being subject to four experiments. Dextran 70 (30 g i.v.) moderately decreased VIII:C and vWF:Ag and slightly increased antithrombin III, also when haemodilution and diurnal variation were considered. Desmopressin (0.3 micrograms/kg BW i.v.), alone as well as in combination with dextran, increased VIII: C, vWF:Ag, protein C and tPA and decreased PAI-1. The combination of desmopressin and dextran stimulated coagulation and fibrinolysis and might be of relevance to surgical blood loss as well as to postoperative thromboembolism.
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PMID:Effects of desmopressin and dextran on coagulation and fibrinolysis in healthy volunteers. 171 90

The levels of hemostatic and fibrinolytic parameters and of molecular markers in venous blood before and after 10 minutes of venous occlusion were measured to evaluate vascular endothelial function in 36 patients with old myocardial infarction, and also in 20 healthy subjects. T-PA activity in the venous blood after occlusion was significantly lower in the patient group compared with the control group, and was lowest in patients with diabetes mellitus. These results were considered to be attributable to elevated PAI-1 and alpha 2 PI levels in these patients. The mean levels of t-PA antigen and VIII R: Ag in venous blood before occlusion were significantly higher in the patient group, but the mean amount of release was no higher in patients than in controls. The plasmin.alpha 2PI complex levels before venous occlusion seemed to indicate the presence of secondary fibrinolysis accompanying hypercoagulability, and the level was significantly higher in patients with diabetes mellitus. Venous occlusion induced the release of t-PA and VIII R: Ag without causing a significant difference in the mean amount of increase of these substances in patient and control groups. However, the lower level of t-PA activity after venous occlusion together with the higher levels of VIII: C, VIII R: Ag, alpha 2PI, PAI-1, and plasmin.alpha 2PI complex before venous occlusion in the patients, indicated that the patient group was in a hypercoagulable and hypofibrinolytic state. In those with diabetes mellitus, the changes were more significant.
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PMID:[Changes induced by venous occlusion in coagulation and fibrinolysis in patients with old myocardial infarction]. 202 72

The circadian fluctuation of hemostasis related parameters was examined on 16 healthy Japanese adults (male 9, female 7). Twenty one parameters were measured in this study, i.e. fibrinogen, the activity of F.II, F.V., F.VII, F.VIII, F.IX, F.X., F.XI, F.XII, antithrombin III, plasminogen, alpha 2-antiplasmin, as well as the antigen level of F.IX, von Willebrand Factor, protein C, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), beta-thromboglobulin, platelet factor 4, fibrinopeptide A, plasmin-alpha 2-antiplasmin complex and FDP. Fluctuation was not significant in almost all of the parameters except F.VIII, F.IX, beta-thromboglobulin, platelet factor 4, tPA and PAI-1. Although the fluctuations of F.VIII, F.IX, beta-thromboglobulin and platelet factor 4 were statistically significant, they remained within the normal ranges. On the other hand, tPA and free PAI-1 showed significant circadian fluctuation, of which levels were highest at 9:00. It was postulated that the significant circadian fluctuation of fibrinolytic activity will be regulated by the balance between tPA and PAI-1 in plasma.
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PMID:Reference values of hemostasis related factors of healthy Japanese adults. I: Circadian fluctuation. 208 89

Excess production of growth hormone (GH) in poorly controlled diabetes is believed to be a causal factor in the development of diabetic angiopathy, the mechanism(s) of which is unknown. The present study was undertaken to determine whether exogenous growth hormone would specifically change some quantities and functional parameters known to often be abnormal in long-standing diabetes and thought to result from the development of vascular lesions in general. The authors studied capillary resistance, factor VIII coagulant antigen (F VIII:Ag), von Willebrand factor (vWf:Ag), fibronectin, fibrinogen, and tissue-type plasminogen activator (t-PA) before, during, and after 1 week's subcutaneous GH administration (6 IU per day divided into two doses). Capillary resistance decreased insignificantly, but returned to higher levels (p less than 0.05) 1 week after withdrawal. F VIII:Ag, vWf:Ag, fibronectin, and fibrinogen all increased significantly during GH treatment. Except for F VIII:Ag, these quantities returned to pre-medication levels 7 days after termination of GH administration. The present results may contribute to the clarification of the role of GH hypersecretion in diabetic microangiopathy and macroangiopathy.
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PMID:Diabetes-like alterations in hemostatic parameters after growth hormone administration for one week in normal man. 252 35


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