Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the relationship between changes in hemostatic factors and postangioplasty restenosis by evaluating plasma levels of P-selectin, beta-thromboglobulin (BTG), and other markers of the coagulation-fibrinolysis system. Seventy-three consecutive patients (56 men and 17 women) undergoing elective percutaneous transluminal coronary angioplasty (PTCA) were enrolled in this study. Patients with acute myocardial infarction within the previous month, unstable angina pectoris, chronic total occlusion, target lesions involving saphenous vein grafts, or coronary artery bypass grafting within the previous 6 months were excluded. Fasting blood samples were obtained before elective PTCA and at follow-up coronary angiography. In patients with restenosis, plasminogen activator inhibitor type-1 (PAI-1) levels were significantly higher (88.2 +/- 36.1 vs 118.5 +/- 50.0 ng/dl; p< 0.05) and plasmin-plasmin inhibitor complex (PIC) levels were significantly lower (0.76 +/- 0.26 vs 0.61 +/- 0.26 microg/ml; p < 0.02) than at baseline. P-Selectin levels were also significantly higher (192 +/- 68 vs 239 +/- 99 ng/ dl; p<0.01) and a positive correlation existed between P-selectin and BTG levels (r= 0.43; p< 0.05). The higher PAI-1 and lower PIC levels in patients with postangioplasty restenosis suggest that impaired fibrinolysis may play a role in the pathogenesis of restenosis, whereas the positive correlation between P-selectin and BTG levels implies a role for activated platelets in restenosis.
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PMID:Postangioplasty restenosis: platelet activation and the coagulation-fibrinolysis system as possible factors in the pathogenesis of restenosis. 912 58

No quantitative, simple and non-radioactive method has been described for measuring the platelet content of experimental thrombi. The aim of the present study was to develop a simple method for quantifying platelets in thrombi formed on thrombogenic surfaces in flowing native human blood. To test the relevance of this new method, the effect of unfractionated heparin on arterial thrombus formation was investigated. Tissue factor (TF)- and collagen-coated coverslips were exposed to non-anticoagulated blood at an arterial wall shear rate (2,600 s(-1)) for 1 to 4 min. Platelet deposition was quantified by measuring the P-selectin (PS) and beta-thromboglobulin (betaTG) content of dissolved plasmin-digested thrombi using immunoenzymoassays; fibrin deposition was determined by measuring the D-dimer levels. These results were compared to those established by morphometrical analysis. Morphometric evaluation showed that fibrin deposition was maximum on TF by 1 min perfusion time. Platelets deposited subsequently and reached a maximum at 3 min. On collagen, platelets deposited directly on the collagen fibrils without detectable fibrin deposit. Platelet deposition increased from 1 to 4 min. Platelet deposition quantified by PS was correlated to the values obtained by morphometry (r = 0.72, r = 0.67, p <0.001, on TF and collagen, respectively). As compared to PS, betaTG measurements gave an underestimation of the size of the thrombus platelet number. Unfractionated heparin infused through a mixing device proximal to the perfusion chamber to obtain plasma concentrations of 0.5, 1 and 3 IU/ml, reduced fibrin deposition on TF-coated coverslips in a dose-dependent manner (77% reduction at 3 IU/ml, p <0.01), but had no significant effect on platelet deposition (33% at 3 IU/ml, p >0.05). In contrast, heparin had no effect on fibrin or platelet deposition on collagen-coated coverslips. Thus, a new quantitative and simple method for measuring platelet deposition in flowing blood has been developed and characterized. Utilizing this system, we have demonstrated that unfractionated heparin did not inhibit arterial thrombus formation either on procoagulant or on proaggregant surface.
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PMID:A new method for quantifying platelet deposition in flowing native blood in an ex vivo model of human thrombogenesis. 945 43

Although platelet activation may play a role in coronary artery spasm, platelets activated following coronary vasospasm have not been clinically detected. We performed flow cytometric analysis of activation-dependent granular proteins, CD62P (P-selectin), CD63, PAC-1 (activated glycoprotein [GP] IIb/IIIa) and thrombospondin on the platelet plasma membrane in patients who exhibited acetylcholine-induced coronary vasospasm and compared findings with those in control patients without vasospasm. We simultaneously investigated the plasma levels of thrombin anti-thrombin III complex (TAT), plasmin alpha2-plasmin inhibitor complex (PIC), and thrombomodulin. In patients with vasospasm, the expression of CD62P, CD63 and PAC-1 on the platelet membrane surface increased in coronary sinus blood samples following coronary vasospasm, although the expression in aortic samples did not change. The TAT level also increased in the coronary sinus after vasospasm. Platelets might be activated by coronary vasospasm within the coronary circulation. The platelet activation process may be modulated by thrombin generation.
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PMID:Detection of platelets activated during acetylcholine-induced coronary vasospasm. 960 37

Polyethylene glycol (PEG)-hirudin is a derivative of hirudin with a long plasma half-life. We have compared the efficacy of PEG-hirudin with unfractionated heparin (UH) in preventing arterial thrombosis. Arterial thrombus formation was induced ex vivo in 12 healthy human volunteers by exposing a tissue factor-coated coverslip positioned in a parallel-plate perfusion chamber to flowing nonanticoagulated human blood drawn directly from an antecubital vein at an arterial wall shear rate of 2600 s-1 for 3.5 minutes. PEG-hirudin, UH, or saline (as control) were administered ex vivo through a heparin-coated mixing device positioned proximal to the perfusion chamber. Platelet and fibrin deposition was quantified by immunoenzymatic measure of the P-selectin and D-dimer content of dissolved plasmin-digested thrombi, respectively. UH was administered to a plasma concentration of 0.35 IU/mL. This concentration prolonged the activated partial thromboplastin time from 32+/-1 seconds to 79+/-4 seconds (P<0.01). UH did not significantly prevent platelet deposition. However, fibrin deposition was reduced by 39% (P<0.05). PEG-hirudin in plasma concentrations of 0.5, 2.5, and 5 microg/mL prolonged the activated partial thromboplastin time to 48+/-2, 87+/-4, and 118+/-4 seconds, respectively. In contrast to UH, PEG-hirudin prevented both platelet and fibrin deposition in a dose-dependent manner with a >80% reduction at 5 microg/mL (P<0.01). Furthermore, the plasma level of PEG-hirudin required to significantly prevent fibrin deposition (0.5 microg/mL) corresponded to a much shorter prolongation of activated partial thromboplastin time (48+/-2 seconds) than that needed for UH (79+/-4 seconds). Thus, our results are compatible with the view that thrombin is greatly involved in recruitment of platelets in evolving thrombi, and that PEG-hirudin is an effective agent for preventing arterial thrombosis in a human ex vivo experimental model.
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PMID:Comparison of the antithrombotic effect of PEG-hirudin and heparin in a human ex vivo model of arterial thrombosis. 1032 89

The alphaIIbeta3 receptor (GPIIb/IIIa) is the only platelet-specific integrin receptor and the most abundant adhesion/aggregation receptor on the surface of human platelets. Since mice are increasingly being used as models of human disease, we analyzed the structure and function of murine platelet alphaIIbeta3, utilizing both beta3 integrin-deficient mice, who have a phenotype that resembles Glanzmann thrombasthenia, and our hamster monoclonal antibody (mAb) 1B5 to murine alphaIIbbeta3. By immunoblot analysis, flow cytometry, and mAb binding studies, mouse platelets express abundant amounts of alphaIIbbeta3 (60-80,000 copies/platelet). Like their human counterparts, murine alphaIIb and beta3 exhibit different electrophoretic motilities under nonreducing (aIIb 135k Da; beta3 92k Da) and reducing (aIIb 120k Da; beta3 108k Da) conditions, and the alphaIIbbeta3 complex is dissociated by EDTA at pH 8 and 37 degrees C. Murine beta3 is less susceptible to proteolysis by plasmin than is human beta3. In addition to defective platelet aggregation, mouse platelets lacking alphaIIbbeta3 and alphaVbeta3 are unable to adhere to fibrinogen and prothrombin, but retain the ability to adhere to fibronectin and collagen. Following platelet activation, beta3-null platelets express slightly less P-selectin than do wild-type mouse platelets. Moreover, beta3-null platelets have altered tyrosine phosphorylation patterns following thrombin- and collagen-induced aggregation. These results suggest fundamental similarities between human and mouse platelet activation and aggregation, but delineate subtle differences that need to be considered when comparing studies from mice and humans.
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PMID:Structure and function of murine alphaIIbbeta3 (GPIIb/IIIa): studies using monoclonal antibodies and beta3-null mice,. 1115 20

To study the in vivo effect of all-trans-retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription-polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As(2)O(3) therapy. The plasma level of P-selectin, TF, thrombin-antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin-antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, alpha(2)-plasminogen inhibitor activity (alpha(2)-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As(2)O(3) therapy downregulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, significantly inhibited coagulation activation, corrected secondary hyperfibrinolysis and the other hemostatic abnormalities, and thus greatly improved the bleeding symptom in early stage of the treatment.
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PMID:Effects of all-trans-retinoic acid and arsenic trioxide on the hemostatic disturbance associated with acute promyelocytic leukemia. 1136 12

Thirty-three subjects with sickle cell disease (SCD), 11 during episodes of pain and 22 during periods without pain, were evaluated for in vivo thrombogenic activities as compared with 10 normal black control subjects. Measurements were performed for (1) platelet surface activation, assessing flow cytometric expression of activated integrin alpha(IIb)beta(3) receptor (GPIIb/IIIa, CD41a) and P-selectin (CD62p); (2) platelet and erythrocyte surface procoagulant activities, measuring flow cytometric binding of activated factor (FVa) and annexin V; (3) plasma levels of platelet-specific secreted proteins platelet factor 4 (PF4) and beta-thromboglobulin (betaTG); (4) plasma markers of thrombin generation, prothrombin activation fragment (F(1.2)), and thrombin: antithrombin complex (TAT); and (5) plasma markers of fibrinolysis, D -dimer, and plasmin:antiplasmin complex (PAP). As compared with control subjects, asymptomatic subjects with SCD demonstrated significantly increased platelet activation (P <.01 for P-selectin and annexin V binding), elevated plasma levels of PF4 and betaTG (P <.01 and P <.03, respectively), and increased plasma concentrations of F(1.2), TAT, PAP, and D -dimer (P <.05 in all cases). During episodes of SCD pain, platelet activation was increased as compared with periods without pain (P <.01 for expression of activated integrin alpha(IIb)beta(3) receptor and P-selectin and binding of FVa and annexin V), erythrocytes expressed procoagulant activities (P <.01 for FVa and annexin V binding), and platelet microparticles appeared in the circulation (3% to 30%; P <.001). SCD pain episodes were associated with elevated plasma levels of F(1.2), TAT, PAP, and D -dimer (P <.05 as compared with asymptomatic intervals). The frequency of pain episodes correlated with enhanced platelet procoagulant activity (r = 0.61, P <.05) and elevated plasma fibrinolytic activity (r = 0.74, P <.01) measured during periods without pain. Plasma fibrinolytic activity was inversely correlated with time to the next pain episode (r = -0.50, P <.05). Thus, asymptomatic subjects with SCD exhibit ongoing platelet activation, thrombin generation, and fibrinolysis that increases during episodes of pain. These changes are predictive of frequency of pain and interval to next pain episode, thereby implicating thrombogenic activity in the development of SCD pain episodes.
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PMID:Thrombogenesis in sickle cell disease. 1138 49

The effects of dietary n-3 fatty acids (n-3FAs) on the frequency of pain episodes and ex vivo blood tests of thrombosis have been evaluated in patients with sickle cell disease (SCD) utilizing a double-blind, olive oil-controlled clinical trial. Dietary n-3FA therapy (0.1 g/kg/d) was provided as menhaden fish oil (0.25 g/kg/d) containing 12% eicosapentaenoic acid (EPA), and 18% docosahexaenoic acid (DHA). Within 1 month dietary n-3FAs exchanged with n-6FAs in plasma and erythrocyte membrane phospholipids (p <0.01 in all cases). Treatment with dietary n-3FAs for 1 year reduced the frequency of pain episodes requiring presentation to the hospital from 7.8 events during the preceding year to 3.8 events/year (p <0.01; n = 5). By contrast, subjects receiving control dietary olive oil (n = 5) experienced 7.1 pain events/year, compared to 7.6 during the previous year (p >0.4). The reduction in episodes in n-3FA-treated subjects was also significant when compared to control subjects (p <0.01). Dietary n-3FA therapy was not associated with hemorrhagic, gastrointestinal or other adverse effects. Compared to 10 asymptomatic African-American controls, sickle cell subjects demonstrated significantly increased pretreatment: 1) flow cytometric expression of platelet membrane P-selectin (CD62p; p <0.01) and annexin V binding sites (p = 0.02); 2) plasma levels of platelet-specific secretory proteins platelet factor 4 (PF4) and beta-thromboglobulin (betaTG) (p <0.01 in both cases); 3) plasma products of thrombin generation, prothrombin fragment 1.2 (F1.2) and thrombin:antithrombin (TAT) complex (p <0.01 in both cases); and 4) plasma levels of thrombolytic products, D-dimer and plasmin:antiplasmin (PAP) complex (p <0.01 in both cases). Treatment with dietary n-3FAs concurrently decreased plasma levels of F1.2, D-dimer, and PAP (p <0.05, compared to olive oil controls), implying that the reduction in pain events was related to n-3FA-dependent inhibition of thrombosis. We conclude that dietary n-3FAs reduce the frequency of pain episodes perhaps by reducing prothrombotic activity in sickle cell disease.
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PMID:Reduction of pain episodes and prothrombotic activity in sickle cell disease by dietary n-3 fatty acids. 1143 3

The aims of this study were to evaluate whether platelets are activated during strenuous exercise in healthy athletes. Also, to determine the impact of plasmin and thrombin activity and catecholamine release. Previous studies have shown activation of the hemostatic system after competitive exercise, but platelet activation was thought to be absent in trained athletes. The impact of thrombin and other potent platelet activators is still a matter for debate. We examined 30 healthy triathletes during a triathlon competition. Flow cytometric detection of CD62p (P-selectin) was used to measure in vivo activation of platelets. Platelet-leukocyte aggregates were also determined. Thrombin concentration was assessed by the thrombin-antithrombin III complex (TAT) and the fibrinolytic state was characterised by the plasmin-alpha2-antiplasmin complex (PAP). Catecholamines were measured by means of high-pressure liquid chromatography. CD62p rose from baseline (2.3%) to 3.4% and was still elevated after 2 hours (3.1%, p = 0.0133). Platelet-leukocyte aggregates were elevated 30 min after exercise (4.3 % vs 3.6%) and decreased significantly after 60 min (2.9 %, p = 0.008). TAT increased from 3.9 microg/l to 8.3 microg/l after competition and to 5.4 microg/l 2 hours later (p < 0.001). PAP increased 10-fold from 350 microg/l to 3,267 microg/l after the triathlon and was still elevated after 2 hours (1,074 microg/l, p<0.001). No linear correlation was found between the hemostatic markers, catecholamines and platelet activation. Platelets, coagulation and fibrinolysis are activated by competitive exercise in athletes, whereby fibrinolytic changes are pronounced. Mechanisms of platelet activation during exercise include phenomena other than plasmatic hemostatic factors and catecholamines.
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PMID:Platelet activation through triathlon competition in ultra-endurance trained athletes: impact of thrombin and plasmin generation and catecholamine release. 1151 Aug 69

Thromboembolic complications are often seen in patients with nephrotic syndrome. Markers of endothelial cell injury [thrombomodulin, intracellular adhesion molecule, vascular cell adhesion molecule, thrombin activatable fibrinolysis inhibitor (TAFI), protein Z, vascular endothelial growth factor, markers of thrombin and plasmin generation] were studied in 22 patients with nephrotic syndrome. All these parameters studied, except protein Z and D-dimers, were significantly higher in patients with nephrotic syndrome, whereas protein Z was significantly lower when compared with the healthy volunteers. None of the endothelial cell markers (thrombomodulin, P-selectin, E-selectin, intracellular adhesion molecule, vascular cell adhesion molecule), thrombin and plasmin generation markers (thrombin-antithrombin complexes, prothrombin fragments 1 + 2, plasmin-antiplasmin complexes, D-dimers), protein C, protein Z, vascular endothelial growth factor, and TAFI concentration and activity were directly correlated with the level of proteinuria, albumin, cholesterol, triglycerides or creatinine, except significant positive correlations between TAFI activity and serum creatinine, E-selectin and albumin as well as negative correlations between plasmin-antiplasmin complexes and proteinuria. In these patients, there is evidence of endothelial cell injury and probably secondary activation of the coagulation cascade. Elevated circulating TAFI antigen and activity might be a new link in the pathogenesis of impaired fibrinolysis and the progression of atherosclerosis in nephrotic syndrome. Protein Z deficiency might also contribute to the enhanced risk of thromboembolic complications in nephrotic syndrome.
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PMID:Markers of endothelial cell injury and thrombin activatable fibrinolysis inhibitor in nephrotic syndrome. 1243 47


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