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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies during recent years have shown the importance of the vascular endothelium in several physiological and pathological circumstances. The culture of endothelial cells has permitted the direct study of endothelial functions. The endothelium is a selective barrier between blood and tissues: the molecules cross it, according to their size, either through the intercellular junctions or through the cells by pinocytotic vesicles. The permeability is modulated by vasomotor agents and modified during endothelial regeneration, especially for the lipids. The endothelium plays a prominent part in the maintenance of the blood flow through its nonthrombogenic properties. It metabolizes circulating thrombogenic substances (arachidonic acid, adenosine diphosphate) and produces potent antiaggregating agents (prostacyclin and adenosine). It may also release a plasminogen activator promoting thrombolysis. The endothelial cells contribute to the formation of the basement membrane by synthesizing collagen and fibronectin, which are involved in platelet adhesion and aggregation to exposed subendothelium. On the other hand, the endothelium has a modulating influence on the local blood flow by producing vasoconstrictors (angiotensin II and III) and vasodilating agents (adenosine and prostacyclin). It is not necessary to elucidate the coordination of these functions and their relationship to the endothelial disorders in vascular diseases.
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PMID:[Vascular endothelium (author's transl)]. 16 42

The effect of long-term ingestion of an anabolic steroid, furazabol, was studied on coagulo-fibrinolytic systems in the rat. During the administration of furazabol at the daily dose of 0.04, 0.2 or 1 mg/rat for 3 months, the most remarkable changes were increase in the plasminogen activator activity in blood and the lung tissue and decrease in plasma fibrinogen level as well as decrease in plasma cholesterol. It was a very important finding that in most of the rats the furazabol treatment was effective in reducing susceptibility to lactic acidosis-induced pulmonary thrombosis. No meaningful changes were observed in other parameters tested including ADP-induced platelet aggregability, plasma recalcification time, plasma plasminogen, plasma antiplasmin activity, plasminogen activator content of tissues other than the lungs and the release of vascular activator induced by venous occlusion. One month after cessation of the furazabol treatment, these altered parameters tended to return to normal. Independently on the furazabol treatment, highly significant positive correlation existed between the plasma activator activity and the pulmonary tissue activator content. This indicated that the major source of plasma activator in the rat was the lung tissue and that the furazabol treatment increased the circulating activator activity through enhancing activator content in the lungs.
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PMID:Enhancement of fibrinolytic and thrombolytic potential in the rat by treatment with an anabolic steroid, furazabol. 103 45

Physicians at the Medical Clinic at the Johannes Gutenberg University in Mainz, Germany, compared data on 6 18-35 year old healthy women who took low-dose estrogen oral contraceptives (OCs) with data on 10 healthy women of same age who did not take OCs and with data on 12 18-35 year old males to examine gender differences of the coagulation system, endogenous fibrinolytic activity, and platelet aggregation under normal conditions and immediately after spiroergometric exercise beyond the anaerobic threshold. This type of exercise considerably boosted tissue plasminogen activator (t-PA) in both men and women (1.6-5.5 IU/ml and 1.8-5.3 IU/ml, respectively; p .005). The increase was not as high in women using the low-dose estrogen OCs as it was for men and both groups combined, however; but the increase was still significant (1.5-3.8 IU/ml; p .005). Plasma lactate levels were 1.1 mmol/l in men and 0.5 mmol/l in both female groups and rose significantly in all 3 groups (about 5.5 mmol/l for men and about 2.5 mmol/l for women; p .001). Exercise beyond the anaerobic threshold did not change plasminogen activator inhibitor-I activities. A marked fall in the ED50 values for adenosine diphosphate (ADP) in men indicated considerable enhancement of platelet activity during exercise (p .05). ADP ED50 values did not change significantly in either women's groups. Yet women who took the OCs had a lower ED50 for ADP than both men and women not taking the OCs, suggesting they were more susceptible to platelet aggregation under control conditions and after exercise. These findings indicated a considerable gender difference in platelet aggregation and activation of the endogenous fibrinolytic system both at rest and during exercise. It was also pointed out that women taking OCs are at even greater risk of developing thrombosis than women not taking OCs.
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PMID:Increase in endogenous fibrinolysis and platelet activity during exercise in young volunteers. 137 84

The mechanisms by which thrombolytic agents affect platelet function are not yet elucidated. The aim of the present study was to investigate the effects of plasmin, generated by thrombolytic agents in plasma, on platelet glycoproteins (GP) Ib and IIb/IIIa. Platelet-rich plasma was incubated with pharmacological amounts of streptokinase, anistreplase and tissue-type plasminogen activator and the platelet surface GP's were investigated with a panel of monoclonal antibodies using flow cytometry. As assessed from the mean fluorescence intensity of incubated and control platelets, no significant changes in the binding of antibodies to GP Ib and GP IIb/IIIa were found. The functional integrity of these glycoproteins was severely impaired by treatment with the thrombolytic agents, as shown by significant inhibition of ADP- and ristocetin-induced platelet aggregation. Experiments with purified plasmin and washed platelets indicated significant degradation of GP IIb/IIIa and upregulation of GP Ib, which is in agreement with previous findings. In addition, platelet activation by plasmin was shown using two monoclonal antibodies to activation-specific antigens. We conclude that degradation of platelet GP's by plasmin offers no likely explanation for the defect in platelet function, which is induced by thrombolytic agents in platelet-rich plasma.
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PMID:Interactions between thrombolytic agents and platelets: effects of plasmin on platelet glycoproteins Ib and IIb/IIIa. 144 May 36

The success of plasminogen activators in recanalizing occluded coronary arteries may be influenced by their effect on blood platelets; however, some previous studies have shown platelet activation by plasmin and thrombolytic agents while others have shown an inhibitory effect. Moreover, it has not been determined whether these effects reflect an alteration of intracellular signal transduction, fibrinogenolysis, degradation of adhesive protein receptors, or a combination of these events. To distinguish among these possibilities, the increase of cytoplasmic [Ca2+] [( Ca2+]i), which is an intracellular marker of platelet activation that precedes fibrinogen binding to the surface of activated platelets, was measured along with aggregation and release of 5-hydroxytryptamine (5-HT) in washed human platelets incubated with plasmin or recombinant tissue-type plasminogen activator (rt-PA). Plasmin (0.1 to 1.0 CU/mL) induced a prompt, concentration-dependent [Ca2+]i increase when added to platelets, but subsequently inhibited the [Ca2+]i increase in response to thrombin or the endoperoxide analog U44069. Platelet aggregation accompanied the [Ca2+]i increase if the platelets were stirred, while the aggregation of platelets unstirred during plasmin incubation was inhibited upon agonist addition and resumption of stirring. The release of 5-HT paralleled the [Ca2+]i increase induced by plasmin and was also inhibited after the subsequent addition of a second agonist. The effects of rt-PA, added with plasminogen (100 micrograms/mL), were similar to those of plasmin, and could be accounted for by the concentration of plasmin generated. The ADP scavengers apyrase and CP/CK each prevented the [Ca2+]i increase, and aggregation caused by plasmin or rt-PA, and also prevented their inhibitory effects on thrombin-induced activation. Thus, plasmin and rt-PA initially activate platelets, inducing a [Ca2+]i increase, and, if the platelets are stirred, aggregation. Such activation is followed by subsequent inhibition of cellular activation by a second agonist; the inhibitory effect is in proportion to the degree of initial activation, and ADP is an important cofactor in both processes. These platelet effects occur at rt-PA concentrations achievable clinically, and may affect the success of therapy with thrombolytic and adjunctive agents.
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PMID:Platelet activation and subsequent inhibition by plasmin and recombinant tissue-type plasminogen activator. 153 Aug 14

Plasmin is known to activate platelets. However, it is not clear whether plasminogen activators as used in thrombolytic therapy can aggregate platelets and how this relates to the ability of each activator to convert plasminogen to plasmin. Urokinase (UK) and streptokinase (SK) activated purified plasminogen (2 microM) in a concentration-dependent manner. The rates of aggregation of washed platelets by the above plasminogen activators and plasminogen were similar to the extent of activation of plasminogen to plasmin in the absence of platelets. UK or SK (0.2 microM) and plasminogen (2 microM) aggregated platelets modified by an ADP affinity analog, 5'-p-fluorosulfonylbenzoyladenosine (FSBA), and cleaved aggregin, a putative ADP receptor, in [3H]FSBA-modified platelets. These results suggest that the effect was independent of ADP. In contrast, incubation mixtures containing only plasminogen (2 microM) and single chain tissue plasminogen activator (sc-tPA) (less than or equal to 0.12 microM) neither activated the zymogen to an appreciable extent nor aggregated platelets. But, in the presence of fibrin(ogen) fragments (tPA-stimulator), a mixture of plasminogen and sc-tPA aggregated unmodified and FSBA-modified platelets, and cleaved aggregin. The results imply that platelets, in the presence of t-PA stimulator, potentiate activation of plasminogen to plasmin by t-PA, as previously reported. P1, Phe-Gln-Val-Val-Cys-(NpyS)-Gly-NH2, (NpyS = 3-nitro-2-thiopyridine), a synthetic hexapeptide capable of binding to and inhibiting calpain, has been shown to inhibit platelet aggregation induced by purified plasmin. P1 inhibited platelet aggregation by plasminogen and any of the three plasminogen activators. Our results show that at plasma concentrations of plasminogen and at levels of UK and SK attained after infusion of these agents during thrombolysis, these mixtures can cause maximum aggregation which may contribute to reocclusion and stenosis following infarct therapy. P1 can effectively inhibit platelet aggregation under such conditions.
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PMID:Aggregation of washed platelets by plasminogen and plasminogen activators is mediated by plasmin and is inhibited by a synthetic peptide disulfide. 153 63

To evaluate the effect of thrombin on the dynamics of thrombolysis, we infused rabbits with heparin or hirudin alone or in conjunction with tissue-type plasminogen activator (t-PA) and monitored the kinetics of fibrinolysis and changes in ex vivo platelet aggregation responses over time. Both heparin and hirudin enhanced total fibrinolysis in an ex vivo arteriovenous shunt preparation: 82 +/- 2% and 79 +/- 2%, respectively, compared with 51 +/- 8% for t-PA alone (P less than 0.05) and 50 +/- 4% for t-PA plus aspirin (p less than 0.05). Heparin coadministered with t-PA significantly reduced the half-time for clot lysis compared with t-PA alone (p less than 0.05), whereas hirudin coadministered with t-PA significantly reduced the half-time for clot lysis compared with that for t-PA alone, t-PA plus aspirin, and t-PA plus heparin (5.5 +/- 0.6 versus 12.1 +/- 2.0 versus 12.6 +/- 2.2 versus 10.0 +/- 0.8 minutes, respectively; p less than 0.05). Both heparin and hirudin prevented the increase in ADP-induced platelet aggregation normally seen with t-PA alone (p less than 0.01 by t test; p less than 0.05 by two-way analysis of variance). These data demonstrate that selective, antithrombin III-independent thrombin inhibitors can enhance the efficacy of thrombolysis by modulating the dynamics of the process and preventing platelet activation associated with plasminogen activator therapy.
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PMID:Effect of thrombin inhibition on the dynamics of thrombolysis and on platelet function during thrombolytic therapy. 155 Dec 6

Both augmentation of thrombin activity and activation of platelets have been reported to accompany administration of plasminogen activators in vivo. To determine whether the platelet activation is a consequence or a cause of the procoagulant effects, we assessed the effects of t-PA on spontaneous activation and aggregation of platelets and on clotting in recalcified human whole blood. Spontaneous activation of platelets occurred in the stirred samples 8.9 +/- 2 minutes (n = 5) after recalcification. Aggregation and clotting followed immediately afterward. Activation, aggregation and clotting were accelerated in a dose-dependent manner by 3 minutes of preincubation with t-PA (2-30 micrograms/ml) before recalcification. The procoagulant effect of t-PA (5 micrograms/ml) was abolished by concomitant incubation with hirudin (0.5 nM) or aprotinin (200 KIU/ml) consistent with the hypothesis of plasmin-mediated evolution of thrombin being responsible for the procoagulant effect. However, platelets could be activated independently by other agonists (collagen, 3 micrograms/ml; and ADP, 25 microM) in the presence of hirudin. Despite the procoagulant effect of t-PA, aggregation to collagen (2-5 micrograms/ml) and PAF (0.9 microM) was diminished in samples incubated with t-PA for 30 minutes (37 degrees C). Fibrinogen degradation products elaborated during this interval (25.6 micrograms/ml; n = 3) were responsible for this anti-aggregatory effect. The results indicate that platelet activation in recalcified whole blood depends on procoagulant effects of t-PA.
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PMID:The dependence of activation of platelets by a plasminogen activator on the evolution of thrombin activity. 172 1

Platelet function was investigated in healthy volunteers and patients with essential hypertension by measurement of thresholds for ADP and adrenaline-induced aggregation and plasma concentrations of platelet factor 4 (PF-4) and beta-thromboglobulin (beta-TG) after administration of antihypertensive drugs. Fibrinolytic activity was investigated by the euglobulin clot lysis time (ECLT) and tissue plasminogen activator (t-PA) activity. Compared to normotensive controls, patients with essential hypertension showed increased aggregation as evidenced by a decrease in ADP thresholds for ex vivo platelet aggregation. ECLT was significantly prolonged and t-PA significantly lowered, indicating impaired fibrinolytic activity in mild hypertension. In different studies, we have shown that various antihypertensive drug regimens differ in their effects on platelet function and fibrinolytic activity when given to healthy volunteers or patients with mild-to-moderate essential hypertension. In normal volunteers, treatment with the calcium antagonists verapamil, nifedipine, and felodipine lowered plasma concentrations of PF-4 and beta-TG, indicating a reduced platelet activity in vivo. Fibrinolytic activity was not influenced by calcium antagonist treatment in the normal volunteers. Interestingly, however, t-PA increased significantly in the hypertensive group. When compared to placebo or beta 1-selective blockers, propranolol, a non-selective beta-adrenergic blocker without partial agonist activity, reduced ADP and adrenaline threshold values for ex vivo platelet aggregation in hypertensive subjects and impaired fibrinolytic activity in the normal volunteers as well as in the hypertensive groups by increasing ECLT and reducing t-PA. Hypothetically, the effects of antihypertensive drugs on platelet function and fibrinolytic activity could be of importance for their proposed actions on cardiovascular morbidity and mortality.
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PMID:Platelet function and fibrinolytic activity in hypertension: differential effects of calcium antagonists and beta-adrenergic receptor blockers. 172 42

Thrombin promotes the formation of arterial thrombi by converting fibrinogen to fibrin and by causing platelets to aggregate. We have examined the combined effects of plasminogen activators and inhibitors of platelet aggregation on the lysis of platelet-rich fibrin clots formed by alpha-thrombin in citrated platelet-rich plasma. The extent of platelet aggregation and clot formation were measured by recording light transmission in an aggregometer. Immediately after the formation of platelet-rich fibrin clots, addition of 2,000 U/ml streptokinase or 50 micrograms/ml recombinant tissue-type plasminogen activator alone resulted in the degradation of polymerized fibrin and the release of trapped platelet aggregates without causing significant platelet deaggregation. Preincubation of the platelet-rich plasma with 20 microM indomethacin for 1 min before thrombin stimulation or simultaneous addition of prostaglandin E1 (10 microM) with the plasminogen activators after thrombin stimulation resulted in spontaneous platelet deaggregation. Because platelet aggregation is, in part, mediated by the binding of Arg-Gly-Asp-containing adhesive proteins to activated platelets, the effect of Arg-Gly-Asp peptides on platelet deaggregation was examined. By itself, Gly-Arg-Gly-Asp-Ser-Pro specifically caused dose- and time-dependent deaggregation of platelet aggregates formed by ADP or by thrombin in the presence of 1 mM Gly-Pro-Arg-Pro, but had no effect on the dissociation of thrombin-induced platelet-rich fibrin clots. In combination with streptokinase or recombinant tissue-type plasminogen activator, Gly-Arg-Gly-Asp-Ser-Pro enhanced the rate of lysis of platelet-rich fibrin clots. The control Gly-Arg-Gly-Glu-Ser-Pro peptide was completely ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid dissociation of platelet-rich fibrin clots in vitro by a combination of plasminogen activators and antiplatelet agents. 176 85


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