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)

In the jugular vein of rabbits thrombus formation was induced by vessel wall damage using a balloon catheter and following reduction of blood flow by 80-90% for 60 min (partial stasis). The blood flow in the vein was measured continuously and the incidence of primary thrombus formation, the time until lysis with recombinant tissue-type plasminogen activator (rt-PA) as well as the incidence of rethrombosis after lysis were determined. At the end of the experiment the wet weight of the thrombus formed inside the vessel was measured. For the determination of haemostaseological parameters blood was drawn from the cannulated femoral artery. Recombinant full-length tissue factor pathway inhibitor (TFPI) was studied with regard to its effect both on primary thrombus formation and on rethrombosis after lysis. In control animals damage of the vessel wall combined with partial stasis led to the formation of occlusive venous thrombi. In vitro bolus injection of TFPI (5, 10, 20 micrograms/kg) at the time of thrombus induction prevented the formation of venous thrombi during the 1 h period of partial stasis. In the subsequent observation period a dose-dependent inhibition of later occurring partial or complete thrombotic occlusion was found. At the dose of 20 micrograms/kg i.v. in all animals TFPI prevented a complete thrombotic occlusion of the vein up to 3 h after stasis. To study the effectiveness of TFPI on rethrombosis after lysis TFPI was injected i.v. after lysis of the thrombus with rt-PA (600 micrograms/kg i.v. bolus + 600 micrograms/kg i.v. infusion over 60 min). In saline treated control rabbits a reocclusion of the vessel was seen in 8 of 10 animals. TFPI (10, 20, 40 micrograms/kg i.v.) injected at the end of rt-PA administration caused a dose-dependent inhibition of thrombotic reocclusion after lysis. At 40 micrograms/kg i.v. the formation of occlusive thrombi was prevented up to 3 h after lysis. TFPI at the doses used caused modest anticoagulant effects in global clotting assays; activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) were only slightly prolonged. A clear and dose-dependent prolongation of clotting times was only seen in the Heptest assay. The results show that the physiologic coagulation inhibitor TFPI acts as a strong antithrombotic agent in an experimental model of venous thrombus formation and thrombotic reocclusion after lysis in rabbits.
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PMID:Recombinant full-length tissue factor pathway inhibitor (TFPI) prevents thrombus formation and rethrombosis after lysis in a rabbit model of jugular vein thrombosis. 890 5

Angiotensin converting enzyme inhibitors (ACE-I) have been reported to prevent the recurrence of cardiovascular events. The mechanism of this decrease, however, can not be completely explained by anti-hypertensive and anti-hypertrophic effects of ACE-I. To investigate the mechanism of this decrease, we studied the regulation of plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (TPA), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) by angiotensin II (Ang II) in cultured rat aortic endothelial cells. Ang II increased PAI-1 and TF mRNA expression without affecting that of TPA or TFPI. These inductions were accompanied by increases in PAI-1 and TF activities and were inhibited by a type I Ang II receptor antagonist. The results suggest that Ang II decreases the antithrombotic properties of endothelial cells which increases the chance of thrombosis. Thus, inhibition of the renin-angiotensin system may be beneficial to prevent thrombus formation in treatment of ischemic heart disease.
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PMID:Angiotensin II increases plasminogen activator inhibitor-1 and tissue factor mRNA expression without changing that of tissue type plasminogen activator or tissue factor pathway inhibitor in cultured rat aortic endothelial cells. 924 56

In previous studies we have shown that, after stimulation by a receptor ligand such as thrombin, tissue-type plasminogen activator (tPA) and von Willebrand factor (vWf) will be acutely released from human umbilical vein endothelial cells (HUVEC). However, the mechanisms involved in the secretion of these two proteins differ in some respects, suggesting that the two proteins may be stored in different secretory granules. By density gradient centrifugation of rat lung homogenates, a particle was identified that contained nearly all tPA activity and antigen. This particle had an average density of 1.11-1.12 g/ml, both in Nycodenz density gradients and in sucrose density gradients. A similar density distribution of tPA was found for a rat endothelial cell line and for HUVEC. After thrombin stimulation of HUVEC to induce tPA secretion, the amount of tPA present in high-density fractions decreased, concomitant with the release of tPA into the culture medium and a shift in the density distribution of P-selectin. vWf, known to be stored in Weibel-Palade bodies, showed an identical distribution to tPA in Nycodenz gradients. In contrast, the distribution in sucrose gradients of vWf from both rat and human lung was very different from that of tPA, suggesting that tPA and vWf were not present in the same particle. Using double-immunofluorescence staining of HUVEC, tPA- and vWf-containing particles showed a different distribution by confocal microscopy. The distribution of tPA also differed from the distribution of tissue factor pathway inhibitor, endothelin-1, and caveolin. By immunoelectronmicroscopy, immunoreactive tPA could be demonstrated in small vesicles morphologically different from the larger Weibel-Palade bodies. It is concluded that tPA in endothelial cells is stored in a not-previously-described, small and dense (d = 1.11-1.12 g/ml) vesicle, which is different from a Weibel-Palade body.
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PMID:An endothelial storage granule for tissue-type plasminogen activator. 931 43

The initial step in atherosclerosis is the rapid targeting of monocytes to the sites of inflammation and endothelial injury. Serum levels of intercellular adhesion molecule-1 were found to be increased in ischaemic heart disease patients and polymorphisms in the E-selectin gene were associated with accelerated atherosclerosis in young (age < 40 years) patients, further suggesting a role of inflammation in atherosclerosis. Cholesterol loading in macrophages was found to induce interleukin-8 expression, suggesting an association between foam cell formation and beta 2-integrin-dependent adhesion of leukocytes. Enhanced endothelium-platelet interaction induced by hypercholesterolaemia is mediated by von Willebrand factor, whereas platelet adhesion to subendothelial matrix is mediated by fibulin-fibrinogen complexes. Activated platelets mediate the homing of leukocytes by interaction with the subendothelial matrix under shear stresses that do not allow neutrophil adhesion. They may also contribute to the oxidative modification of LDL, provide a source of lipids for foam cell generation and contribute to smooth muscle cell proliferation. Oxidized LDL induces tissue factor in macrophages that also provide sites for fibrin polymerization and decreases the anticoagulant activity of endothelium by interfering with thrombomodulin expression and inactivating tissue factor pathway inhibitor. Intravascular fibrinolysis induced by tissue-type plasminogen activator or urokinase may contribute to the initiation of atherosclerosis by inducing P-selectin and platelet activating factor as well as to plaque rupture, either directly or indirectly, by activating metalloproteinases. Plasminogen activator inhibitor-1 inhibits smooth muscle cell migration and, in the presence of vitronectin, promotes the clearance of thrombin by LDL receptor-related protein at sites of endothelial injury.
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PMID:Thrombosis and atherosclerosis. 933 57

It is widely recognized that thrombosis is the major event in the evolution of stable vascular disease to unstable ischaemic syndromes including myocardial infarction and stroke. The purpose of this case-control study was to establish clinical and laboratory data on the possible relationship between specific components of the haemostatic system and coronary heart disease. The procoagulant activity (PCA) of peripheral monocytes and polymorphonuclear neutrophils was assessed in 21 males who had suffered a myocardial infarction (MI) and in age-matched controls. In addition, total factor VII activity, fibrinogen, tissue factor pathway inhibitor (TFPI). D-dimers, tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), tumour necrosis factor-alpha (TNF-alpha) and full blood counts were measured. Post MI patients had significantly higher monocyte PCA, higher plasma concentrations of TFPI, fibrinogen, t-PA, T/P100 and also higher total white blood cell and neutrophil counts compared to age-matched controls. This elevated procoagulant state in post MI patients could further exacerbate the disease process and increase the risk of subsequent acute ischaemic events.
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PMID:Monocyte tissue factor-like activity in post myocardial infarction patients. 969 80

We review laboratory tests that evaluate thrombogenesis during acute coronary syndromes. These tests have been found to be valuable research tools in more clearly understanding the pathophysiology of acute coronary syndromes. In particular, we describe tissue factor, tissue factor pathway inhibitor, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrinopeptide A, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), t-PA-PAI complex, Bbeta 15-42-related peptides, fibrinogen degradation products, fibrin degradation products, D-dimer, platelet factor 4, beta-thromboglobulin, 5-hydroxytryptamine, thromboxane B2, prostacyclin, endothelin, angiotensin-converting enzyme, soluble thrombomodulin, C1-esterase inhibitor, anaphylotoxins C3a, C4a, and C5a, bradykinin, tumor necrosis factor, leukotriene C4, platelet activating factor, anti-phospholipid antibody, and von Willebrand factor. Some of these tests may prove to be useful in clinical diagnosis and management of acute coronary syndromes. Clinical outcome studies are needed to determine which tests may be cost effective and medically useful.
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PMID:Useful laboratory tests for studying thrombogenesis in acute cardiac syndromes. 970 94

Vascular endothelial cells play a critical role in the regulation of coagulation and fibrinolysis by controlling the expression of tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), and tissue type plasminogen activator (TPA). Vasoconstrictors can induce TF and PAI-1 expression without changing the TFPI or TPA expression level. Vasodilators can not alter that of TFPI or TPA, but they inhibit the induction of TF or PAI-1 by vasoconstrictors. These results suggest that by making TF predominant to TFPI and PAI-1 to TPA, vasoconstrictors cause the vascular endothelial cells to become thrombogenic and vasodilators inhibit this process. The thrombogenicity by vasoconstrictors may be originally involved in the protective mechanisms against bleeding, and antithrombogenicity by vasodilators may be originally a part of the protective mechanisms against stasis. In treating hypertension, it is necessary to consider this thrombogenicity by vasoconstrictors in order to avoid iatrogenic thrombotic disease.
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PMID:[The regulation of blood coagulation and fibrinolysis by vascular endothelial cells]. 1042 46

The low density lipoprotein receptor-related protein (LRP) is a multifunctional endocytic cell-surface receptor that binds and internalizes a diverse array of ligands. The receptor contains four putative ligand-binding domains, generally referred to as clusters I, II, III, and IV. In this study, soluble recombinant receptor fragments, representing each of the four individual clusters, were used to map the binding sites of a set of structurally and functionally distinct ligands. Using surface plasmon resonance, we studied the binding of these fragments to methylamine-activated alpha(2)-macroglobulin, pro-urokinase-type plasminogen activator, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1, t-PA.plasminogen activator inhibitor-1 complexes, lipoprotein lipase, apolipoprotein E, tissue factor pathway inhibitor, lactoferrin, the light chain of blood coagulation factor VIII, and the intracellular chaperone receptor-associated protein (RAP). No binding of the cluster I fragment to any of the tested ligands was observed. The cluster III fragment only bound to the anti-LRP monoclonal antibody alpha(2)MRalpha3 and weakly to RAP. Except for t-PA, we found that each of the ligands tested binds both to cluster II and to cluster IV. The affinity rate constants of ligand binding to clusters II and IV and to LRP were measured, showing that clusters II and IV display only minor differences in ligand-binding kinetics. Furthermore, we demonstrate that the subdomains C3-C7 of cluster II are essential for binding of ligands and that this segment partially overlaps with a RAP-binding site on cluster II. Finally, we show that one RAP molecule can bind to different clusters simultaneously, supporting a model in which RAP binding to LRP induces a conformational change in the receptor that is incompatible with ligand binding.
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PMID:The second and fourth cluster of class A cysteine-rich repeats of the low density lipoprotein receptor-related protein share ligand-binding properties. 1053 29

In the present study, we demonstrate that brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) interact with angiotensin II (Ang II) in regulative blood coagulation and fibrinolysis by suppressing the expressions of both tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) induced by Ang II. The expressions of TF and PAI-1 mRNA were analyzed by northern blotting methods, and the activities of TF on the surface of rat aortic endothelial cells (RAECs) and PAI-1 in the culture media were respectively measured by chromogenic assay. Both BNP and CNP suppressed the expressions of TF and PAI-1 mRNA induced by Ang II in a time- and concentration-dependent manner via cGMP cascade, which suppressions were accompanied by respective decrease in activities of TF and PAI-1. However, neither the expression of tissue factor pathway inhibitor (TFPI) nor tissue-type plasminogen activator (TPA) mRNA was affected by the treatment of BNP and CNP.
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PMID:Natriuretic peptides regulate the expression of tissue factor and PAI-1 in endothelial cells. 1059 44

Not only angiotensin II (Ang II) but also other angiotensin metabolites such as angiotensin I (Ang I), angiotensin III (Ang III), angiotensin IV, or angiotensin 1-7 have recently been reported to have various activities. Few data, however, are available on the regulation of thrombus formation. In this study, we investigated the effects of angiotensin metabolites on the mRNA expression of tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), and tissue type plasminogen activator (TPA) in cultured rat aortic endothelial cells. None of the used angiotensin metabolites altered TFPI or TPA mRNA expression levels. Ang I, Ang II, and Ang III made TF and PAI-1 mRNA inductions which were inhibited by an selective antagonist of angiotensin II type 1 receptors. These metabolites made TF predominant to TFPI or PAI-1 to TPA, and could render endothelial cells thrombogenic.
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PMID:The effects of angiotensin metabolites on the regulation of coagulation and fibrinolysis in cultured rat aortic endothelial cells. 1059 47


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