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)

Fifty-one patients with mild hypertension were evaluated in relation to the plasma concentrations of coagulation and fibrinolysis factors as well as for the aggregability of their platelets. In a considerable number of the patients (18/51), a significantly enhanced in vitro ADP (2 mumol/l)-induced aggregation was found. In the coagulation line significant increases could be demonstrated in fibrinogen, fibrin monomers and thrombin-antithrombin III. The fibrinolysis system showed significant increases for D-dimers, tissue plasminogen activator antigen and plasminogen activator inhibitor, whereas the tissue plasminogen activator activity was significantly diminished. Remarkably, there seems to be a discrepancy between the (low) tissue plasminogen activator activity and the (higher) plasminogen activator antigen concentration. Alterations in the plasma concentrations of the investigated coagulation and fibrinolysis factors and in the aggregability of the platelets are indicative of an involvement of coagulation, fibrinolysis and platelets in hypertension, which can be considered as partial risk factors for thrombophilia.
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PMID:Plasma concentration of coagulation and fibrinolysis factors and platelet function in hypertension. 191 85

The aim of this study was to evaluate the effects of a preparation of low molecular weight heparan sulphate (LMW-HS) on the fibrinolytic system. Twenty-five healthy volunteers received LMW-HS by mouth in three separate experiments. In the first experiment, 10 volunteers received either 80 mg LMW-HS or placebo in a single-blind cross-over study; blood samples were taken before and 1, 2, 3 and 6 h after treatment. LMW-HS caused an increase in global fibrinolysis, the effect being greatest after 2-3 h and disappearing by 6 h. However, neither plasminogen activator activity nor tissue-type plasminogen activator (tPA) antigen levels were changed. In the second experiment, daily doses of 80 mg LMW-HS were administered to 10 volunteers for 7 days; this regimen did not produce a statistically significant increase in fibrinolytic activity for the whole group although some individuals did respond markedly. In the third experiment, 160 mg LMW-HS administered to five volunteers did not affect ADP- and collagen-induced platelet aggregation. In vitro, LMW-HS added to plasma at concentrations of 20 and 30 micrograms/ml, brought about a significant increase in apparent plasminogen activator activity. These results suggest that the increased fibrinolytic activity seen after LMW-HS is due to the recruitment of additional amounts of tPA in the ex vivo test system. LMW-HS had no effect on plasminogen activator inhibitor.
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PMID:In vivo and in vitro effects of low molecular weight heparan sulphate on the human fibrinolytic enzyme system. 193 31

We evaluated the effect of the RGD-containing peptide, echistatin, on thrombolysis time and acute reocclusion in a canine model of coronary thrombosis/thrombolysis. Occlusive thrombus formation was induced by electrical injury, via a stimulating electrode, to the endothelial surface of the circumflex coronary artery in the open-chest, anesthetized dog in the presence of a critical stenosis. Fifteen minutes after occlusive thrombus formation, dogs received either an intravenous infusion of vehicle (saline at 0.1 ml/min) or echistatin (15 micrograms/kg/min i.v.). Heparin was given as an initial bolus (100 U/kg i.v.) 15 min after thrombus formation and repeated at hourly intervals (50 U/kg). This dose of heparin increased activated partial thromboplastin time to 1.5- to 2.5- fold over control. Thrombolysis was induced with recombinant tissue-type plasminogen activator (tPA) at a total dose of 1 mg/kg, intravenously administered over 90 min with 10% given as an initial bolus. The vehicle-treated animals reperfused at 48 +/- 9 min with a reperfusion incidence of 60% (3/5). The echistatin-treated animals reperfused at 46 +/- 5 min with a reperfusion incidence of 100% (5/5). After stopping the tPA infusion, acute reocclusion occurred in 100% (3/3) of the vehicle-treated dogs and in only 20% (1/5) of the echistatin-treated dogs. Echistatin caused a greater than 5-fold increase in buccal mucosa bleeding time and almost completely inhibited ex vivo platelet aggregation to ADP, collagen, and U-46619. Residual thrombus wet weight, determined at the end of the experiment, was significantly lower for the echistatin group (2.1 +/- 0.2 mg) compared to the vehicle group (5.8 +/- 0.7 mg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of reocclusion following tissue type plasminogen activator-induced thrombolysis by the RGD-containing peptide, echistatin, in a canine model of coronary thrombosis. 194 98

Aspirin has been shown to be beneficial in the prophylaxis of arterial thromboembolic disease. The rationale for its use as an antithrombotic drug lies in its inhibition of thromboxane A2-dependent platelet function. However, the effect of aspirin on coagulation and fibrinolysis during chronic therapy has not been studied. We have measured a range of haemostatic and platelet functions in 49 patients with transient ischaemic attacks randomly allocated to aspirin 300 mg a day, aspirin 1,200 mg a day or placebo. All had been taking their allocated treatment for between 9 months and 4 years prior to investigation. Bleeding time was prolonged, serum thromboxane diminished and platelet aggregation to arachidonic acid but not ADP was abolished by both 300 mg and 1,200 mg aspirin, in a non-dose dependent fashion. Serum salicylate increased with the dose of aspirin ingested. No effect was seen with either dose of aspirin on urinary thromboxane and 6-keto-PGF1 alpha excretion, or on coagulation. Patients taking 1,200 mg aspirin a day had a lower haemoglobin and packed cell volume, lower resting fibrinopeptide A concentration and lower basal plasminogen activator activity than those on placebo. Response to venous occlusion was normal in all groups. The results suggest 300 mg and 1,200 mg aspirin have an equivalent platelet inhibitory effect but 1,200 mg aspirin causes greater gastro-intestinal blood loss.
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PMID:Coagulation, fibrinolytic and platelet function in patients on long-term therapy with aspirin 300 mg or 1,200 mg daily compared with placebo. 207 96

Coronary artery rethrombosis can complicate initially effective thrombolytic therapy. Platelets interacting with injured vascular endothelium in a region along the coronary artery with reduced luminal cross-sectional area contribute to rethrombosis. The purpose of this study was to investigate the potential of the F(ab')2 fragment of the murine monoclonal antibody 7E3 [7E3 F(ab')2] to prevent rethrombosis after intracoronary clot lysis with recombinant tissue-type plasminogen activator (rt-PA) in an experimental model. The 7E3 F(ab')2 binds to the platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa), thereby preventing platelet-fibrinogen interaction and intravascular thrombus formation. Experimental coronary artery thrombosis was produced in the anesthetized dog by application of direct anodal current to the intimal surface of the left circumflex coronary artery in the region of an external stenosis. Lysis of the established intracoronary thrombus was achieved with the intravenous administration of rt-PA (25 mg) after which the animals were randomized into two groups. Group 1 (n = 10) served as the control, receiving the saline diluent, and group 2 (n = 9) received 7E3 F(ab')2, given as a single intravenous injection (0.8 mg/kg). The times required for occlusive thrombus formation, rt-PA-induced thrombolysis, and rethrombosis (if it occurred) were similar in the animals treated with saline and those treated with 7E3 F(ab')2. The initial left circumflex coronary artery blood flow was similar in both groups but decreased to a negligible level in group 1. In group 2, left circumflex coronary artery blood flow declined modestly (24 +/- 2 to 10 +/- 2 ml/min). Rethrombosis occurred in all animals in group 1 but in only two of nine animals in group 2 (p less than 0.05). Oscillations in coronary blood flow preceded rethrombosis in group 1, whereas 7E3 F(ab')2 stabilized left circumflex coronary artery blood flow patterns during the course of teh experimental protocol (5.2 +/- 0.9 vs. 0.7 +/- 0.4 oscillations, respectively; p less than 0.05). Thrombus mass recovered from the left circumflex coronary artery at the conclusion of each experiment was greater in group 1 as compared with group 2 (7.0 +/- 2.3 vs. 1.5 +/- 0.7 mg, respectively; p less than 0.05). The area of left ventricle at risk for infarction was similar in both groups but infarct size, infarction/at risk assessed histochemically, was larger in group 1 than group 2 (35 +/- 9% vs. 6 +/- 4%, respectively; p less than 0.05). Platelet aggregation induced by ADP and arachidonic acid was similar at baseline for all of the animals.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antiplatelet antibody [7E3 F(ab')2] prevents rethrombosis after recombinant tissue-type plasminogen activator-induced coronary artery thrombolysis in a canine model. 210 75

Two in vitro models of coronary thrombolysis in man, i.e. dislodgement of thrombi formed from non-anticoagulated human blood, either by (i) shear-stress or (ii) interaction of platelets with type I collagen fibre, were studied. Heparinization (1 U/ml) of blood prior to thrombus formation by (i) strongly inhibited spontaneous dislodgement (P less than 0.0001). Heparin (1 U/ml), when added with streptokinase (SK) or tissue-type plasminogen activator (rt-PA) prior to thrombus formation, considerably delayed thrombolysis. Furthermore, thrombolysis occurred much earlier when thrombi were perfused with SK or rt-PA in native than in heparinized blood. Heparin inhibited binding of 125I-rt-PA (17%, P less than 0.02) and plasminogen (88%, P less than 0.0005) to platelets activated by ADP in citrated platelet-rich plasma. We conclude that heparin interferes with the fibrinolytic system at the surface of activated platelets. Our findings suggest that heparin administration prior to thrombolytic therapy for acute myocardial infarction should be questioned.
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PMID:Heparin inhibits spontaneous thrombolysis and the thrombolytic effect of both streptokinase and tissue-type plasminogen activator. An in vitro study of the dislodgement of platelet-rich thrombi formed from native blood. 210 72

SK, t-PA or APSAC were incubated in human plasma (adjusted to 300,000 platelets/mm3), in vitro, for up to 90 minutes using concentrations which were equivalent to those achieved in the treatment of AMI patients. Aggregation was measured in response to ADP and collagen. SK inhibited platelet aggregation after a 60 minute incubation. t-PA was less inhibitory and significant effects were only achieved on extended incubation with a higher concentration of activator. APSAC markedly inhibited platelet aggregation in response to both ADP and collagen and the inhibition was achieved earlier than with SK. The difference in temporal response between APSAC and SK was not attributed to differences in systemic plasminogen activation. There was no influence of anti-SK antibody (IgG) on the platelet function response to APSAC or SK. Aspirin inhibited second phase aggregation induced by ADP but even in the presence of aspirin, the net inhibition of platelet aggregation was greater for APSAC than for SK. This marked effect of APSAC on platelet aggregation helps to explain the high initial patency and low re-occlusion rates seen when APSAC is administered to AMI patients.
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PMID:Comparison of the effects of streptokinase, t-PA and APSAC on human platelet aggregation in vitro in the absence and presence of aspirin. 212 20

To examine the temporal effects of plasmin generated in vivo on platelet function, we infused tissue-type plasminogen activator (t-PA) in rabbits over 3 hours and measured ex vivo platelet aggregation. We noted an initial increase in the aggregation response to ADP occurring 30 minutes after the start of infusion. This enhanced response was short-lived and by 180 minutes was reduced, compared with pretreatment levels. Baseline aggregation response was restored by 240 minutes. This pattern of aggregation response to t-PA infusion was also seen with thrombin as the agonist. Coinfusion of either prostaglandin I2 or prostaglandin E1 abolished the initial hyperaggregable phase induced by t-PA; the hypoaggregable phase occurred earlier (after 60 minutes) and persisted throughout the 1-hour recovery period. Similarly, streptokinase infused for 1 hour also increased platelet aggregation at early times and then reduced aggregation responses after the first hour. Plasma plasmin activity increased as expected with t-PA infusion alone, peaking at 30 minutes and returning to baseline by the first hour. Interestingly, prostaglandin E1 blunted the rise in plasma plasmin activity. This same dose of prostaglandin E1 or prostaglandin I2 used alone did not appreciably alter platelet function at any time during the experiment. Our data show that therapeutic doses of t-PA or streptokinase produce a biphasic effect on platelet aggregation response in the rabbit. Coinfusion of either of the antiplatelet agents, prostaglandin E1 or prostaglandin I2, abolishes the hyperaggregable phase and prolongs the inhibitory effects on platelet aggregation produced by t-PA. These data suggest that the effects of thrombolytic agents on platelet function are complex and can be modulated by antiplatelet prostaglandins.
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PMID:Temporal effects of thrombolytic agents on platelet function in vivo and their modulation by prostaglandins. 214 37

To elucidate interactions responsible for inhibition of aggregation of platelets in platelet-rich plasma (PRP) harvested from whole blood preincubated with t-PA, experiments were performed with PRP and washed platelets under diverse conditions of preincubation. Both ADP and collagen induced aggregation were inhibited in PRP unless aprotinin had been added to the preincubated whole blood concomitantly with t-PA. However, in washed platelets prepared after the same exposure aggregation was intact. When washed platelets were supplemented with fibrinogen degradation products (FDPs) in concentrations simulating those in whole blood preincubated with t-PA, aggregation induced with either ADP or collagen was inhibited. Thus, the inhibition in PRP depended on generation of FDPs by activated plasminogen. The functional integrity of surface glycoprotein (GP) IIb/IIIa receptors in washed platelets was documented by autoradiography after SDS-PAGE of surface labeled GPs and by fibrinogen binding despite preincubation of the whole blood or washed platelets themselves with t-PA and plasminogen as long as exogenous calcium (greater than or equal to 0.1 microM) was present. In contrast, when calcium was absent, the platelet GP IIb/IIIa receptor was rendered susceptible to degradation by plasmin, and aggregation was inhibited by preincubation at 37 degrees C even if aprotinin was present when aggregation was being assayed. These observations reconcile disparate results in the literature from studies in vivo and in vitro by demonstrating that inhibition of aggregation of platelets in PRP and in whole blood reflects indirect effects of plasminogen activation rather than direct effects of t-PA or plasmin on the platelets themselves.
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PMID:The nature of interactions between tissue-type plasminogen activator and platelets. 214 66

When a variety of ferric chelates are reacted with hydrogen peroxide in phosphate buffer deoxyribose is damaged and this damage is protected against by formate, thiourea and mannitol. Damage done by ferric complexes of citrate, EDTA, NTA, EGTA and HEDA is substantially inhibited by superoxide dismutase (SOD) whereas complexes of PLA, ADP and CDTA are moderately inhibited by SOD. The effects of SOD argue against hydrogen peroxide acting as a reductant in Fenton chemistry driven by ferric complexes and hydrogen peroxide. EDTA has proved to be a useful model for Fenton chemistry that is inhibited by SOD although, it is not unique in this respect.
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PMID:Superoxide-dependent formation of hydroxyl radicals from ferric-complexes and hydrogen peroxide: an evaluation of fourteen iron chelators. 216 86


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