Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the relationships between albuminuria, tissue factor-induced coagulation, and endothelial cell dysfunction in 67 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were divided into three groups on the basis of their urinary albumin excretion rate (AER). To assess the early phase of tissue factor-induced coagulation, activated factor VII (FVIIa) levels in plasma were measured by a direct fluorogenic assay. As markers of endothelial cell dysfunction, levels of von Willebrand factor (vWF), tissue-type plasminogen activator-plasminogen activator inhibitor-1 (TPA-PAI-1) complex, PAI-1, and tissue factor pathway inhibitor (TFPI) were measured. FVIIa levels were increased in normoalbuminuric NIDDM patients (AER < 15 micrograms/min) when compared with normal control subjects. This FVIIa increase was accompanied by an increase in thrombin-antithrombin III complex (TAT) levels, indicating increased activation of coagulation even in normoalbuminuric patients. In NIDDM patients with microalbuminuria (AER = 15-200 micrograms/min), the FVIIa level, the FVIIa-FVII antigen (Ag) ratio (an indicator of activation of FVII zymogen to FVIIa), and the TAT level were further increased. This group also had higher levels of endothelial cell-derived factors (vWF, TPA-PAI-1 complex, and PAI-1) than the control group. The levels of endothelial cell-derived factors (including TFPI) were highest in the NIDDM patients with overt albuminuria (AER > 200 micrograms/min). In all 67 diabetic patients, AER showed a strong positive correlation with FVIIa (r = .574, P < .0001) and a weakly but still significant correlation with FVIIa-FVII:Ag (r = .365, P = .01), vWF (r = .315, P < .01), and TAT (r = .323, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria. 762 4

HMEC-1 is a SV-40T transfected human microvascular endothelial cell line that constitutively expresses RNA transcripts for plasminogen activator inhibitor 1 (PAI-1), tissue-type plasminogen activator (t-PA), protein S (PS), von Willebrand factor (vWF), and thrombomodulin. Tissue factor (TF) can be induced in response to stimulation with tumor necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL-1alpha) and phorbol 12-myristate 13-acetate (PMA). Proteins corresponding to PAI-1, t-PA, protein S and vWF genes were constitutively released in the culture supernatant. This cell line is a model that will be useful to investigate coagulation/fibrinolytic properties of microvascular endothelium.
 ...
PMID:Hemostatic properties of the SV-40 transfected human microvascular endothelial cell line (HMEC-1). A representative in vitro model for microvascular endothelium. 767 2

Herpes simplex virus (HSV) infection is histopathologically associated with vascular injury, fibrinoid necrosis and inflammatory cell infiltrates. We have previously shown in vitro that HSV infection of human umbilical vein endothelial cells (HUVEC) promotes a procoagulant phenotype manifest by the induction of tissue factor, the loss of thrombomodulin, and an increase in platelet adhesion. In these studies we examined the effects of HSV infection on HUVEC plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA). HSV infection caused the loss of PAI-1 in the extracellular matrix (ECM) and that released into the supernatant of HUVEC. Both activity and antigen levels of the Serpin inhibitor are diminished as a result of HSV infection. The loss of inhibitor is not secondary to diminished vitronectin (Vn), the primary binding protein of PAI-1 in the ECM, but appears to be secondary to decreased synthesis at the RNA level. Tissue plasminogen activator (t-PA) synthesis is also decreased in endothelial HSV infection. PAI-1 loss may further promote a procoagulant phenotype in HSV infection in vivo.
 ...
PMID:Herpes simplex virus decreases endothelial cell plasminogen activator inhibitor. 768 40

Endothelial cells are responsible for the secretion or surface expression of a wide variety of mediators involved in the control of thrombosis. These include von Willebrand factor, prostacyclin, nitric oxide, thrombomodulin, tissue-type plasminogen activator and its inhibitor, tissue factor and the tissue factor pathway inhibitor. The production of each of these can be modulated; in some cases very rapidly in response to external stimuli, in other cases more slowly. Thrombin is a key stimulus, which affects the production of almost all of these mediators. In addition, several cytokines and bacterial endotoxins shift the balance of endothelial mediator secretion from the basal anticoagulant profile towards a procoagulant profile.
 ...
PMID:Vessel wall interactions regulating thrombosis. 780 30

Upon stimulation with lipopolysaccharides (LPS), monocytes are able to produce tissue factor (TF), the most powerful physiological procoagulant substance known. In several assay systems LPS bound to lipoprotein has been reported to be less active than unbound LPS in stimulating monocytes. In the present study the LPS-induced TF activity was, however, not prevented by lipoproteins (VLDL, LDL, HDL). In fact, the very low density (VLDL) fraction further increased the TF inducing capacity of LPS. The lipoproteins per se mediated reduced plasminogen activator (PA) production in monocytes. LPS had an even more and significant depressing effect on PA production, which was not further decreased in the presence of lipoproteins. Furthermore, LPS-induced release of tumour necrosis factor (TNF), a marker of monocyte activity, was not inhibited by lipoproteins. Our experiments suggest that lipoproteins do not render LPS less effective in stimulating TNF release, procoagulant and fibrinolytic activities in human monocytes.
 ...
PMID:Lipoproteins do not modulate the tissue factor activity, plasminogen activator or tumour necrosis factor production induced by lipopolysaccharide stimulation of human monocytes. 780 80

The epithelial lining of the airways is subject to injury through several processes, including infections, bronchiolitis, and fume exposures. Because airway fibrin deposition influences the course of local injury, we examined how two inflammatory cytokines influenced fibrin formation and clearance in human tracheal epithelial cells (TEC). TEC were treated with transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha). TNF-alpha increased release of tissue factor (TF)-related procoagulant activity that, through generation of factor Xa, promotes assembly of the prothrombinase complex at the cell surface. Fibrinolytic activity was plasminogen dependent and due to both urokinase (uPA) and tissue plasminogen activator (tPA). The cells expressed plasminogen activator inhibitor 1 (PAI-1), but relatively little PAI-2. Depression of fibrinolysis by TGF-beta correlated with increased PAI-1. Conversely, TNF-alpha increased plasminogen activator (PA) activity due to increased uPA. Fibrinolytic activity was inhibited by actinomycin D and cyclohexamide, but changes in mRNAs for uPA, tPA, PAI-1, and TF by either cytokine were not appreciable. PAI-2 mRNA was not found. The data indicate that TGF-beta decreases the fibrinolytic capacity of TEC, suggesting that this cytokine promotes fibrin retention. TNF-alpha increases expression of both procoagulant and fibrinolytic activities; this differential regulation could favor both pericellular fibrin formation and dissolution.
 ...
PMID:Effects of TGF-beta and TNF-alpha on procoagulant and fibrinolytic pathways of human tracheal epithelial cells. 781 Jun 74

Healthy endothelium is a metabolically active interface between the blood and extravascular tissues. Its intimal surface is anticoagulant and antithrombotic, and it secretes a variety of molecules involved in regulating platelet function and blood coagulation. The rapid interactions between platelets, their secreted components, or thrombin and endothelial cells at sites of vessel damage ensure the local secretion of mediators such as prostacyclin and nitric oxide that limit the intravascular growth of the haemostatic plug. There is considerable evidence that a decreased ability of endothelial cells to synthesize NO contributes to the pathogenesis of arterial disease. Local deficiency of PGI2 synthesis has also been implicated in the thrombotic problems in haemolytic uraemic syndrome. Endothelium is also the source of circulating von Willebrand factor, important for efficient platelet adhesion. Chronically elevated plasma levels of vWF in a series of diseases where there is vascular pathology apparently reflect endothelial cell damage or activation, and may contribute to the prothrombotic tendency they exhibit. They may be compounded by decreased levels of the surface anticoagulant thrombomodulin, if the increased concentrations of the soluble forms of thrombomodulin detected in the circulation under similar conditions are a reflection of loss from the endothelium. Further alterations of function in a procoagulant/prothrombotic direction take place when endothelial cells are exposed to certain cytokines or lipopolysaccharide. Tissue factor synthesis is induced, thrombomodulin expression is decreased, and there is enhanced sensitivity of vWF secretion. In addition, the balance of tissue-type plasminogen activator and plasminogen activator inhibitor type I secretion is changed in favour of the latter. These processes are each likely to contribute to the occurrence of disseminated intravascular coagulation which can accompany septic shock.
 ...
PMID:Endothelial cell function and thrombosis. 784 94

Serine proteinase inhibitors play a major role in the turnover of connective tissues. In this study, we isolated and determined partial amino-terminal amino acid sequence of trypsin/elastase/plasmin inhibitors (M(r) 33,000 and 31,000) from the extracellular matrix of SV40-transformed human skin fibroblasts. The antitrypsin activity of the inhibitors was monitored by substrate reverse zymography. Polyclonal antisera to alpha 1-antitrypsin, alpha 1-antichymotrypsin, alpha 2-antiplasmin, inter-alpha-trypsin inhibitor, plasminogen activator inhibitors-1 and -2, and a monoclonal antibody to protease nexin-1 did not label the 33-, 31-, and 27-kDa inhibitors. A computer search for amino acid sequence homology indicated that the 31-kDa inhibitor is novel. In contrast, the sequence of the 33-kDa inhibitor shared 70 to 90% homology with the amino-terminal sequence of a recently characterized 32-kDa trypsin/tissue factor inhibitor called tissue factor pathway inhibitor-2. The 33- and 31-kDa inhibitors bind to heparin-Sepharose and were recovered from the affinity beads as well as from the t12 FB extracellular matrix with 1 M NaCl. Based on these results, we propose that the extracellular matrix of human mesenchymal cells sequester a family of novel serine proteinase inhibitors.
 ...
PMID:Novel extracellular matrix-associated serine proteinase inhibitors from human skin fibroblasts. 787 99

Endothelial cell products contribute to many aspects of the regulation of haemostasis. They include potent inhibitors of platelet aggregation (prostacyclin and nitric oxide) rapidly released in response to agonists such as thrombin. Similar agonists also induce the formation of platelet-activating factor by endothelium. Endothelial cell surface ectonucleotidase enzymes control the catabolism of platelet-active adenine nucleotides. The main source of the circulating coagulant cofactor von Willebrand factor is the endothelium, where it is stored in granules for agonist-triggered exocytosis and also secreted constitutively. Surface anticoagulant activities are due to the presence of antithrombin and thrombomodulin. Endothelial cells also secrete plasminogen activator and its inhibitor. Many of these reactions are significantly modulated by exposure of endothelium to cytokines or bacterial endotoxin, the most striking example being the new synthesis and surface expression of the procoagulant tissue factor (thromboplastin).
 ...
PMID:The control of production and release of haemostatic factors in the endothelial cell. 802 46

An experimental disseminated intravascular coagulation (DIC) was induced in female CD rats by the intravenous administration of living bacteria (9.5 x 10(7) cfu Klebsiella pneumoniae), sublethal (5 mg/kg) or lethal (50 mg/kg) lipopolysaccharide (LPS), or tissue factor (1.5 micrograms/kg i.v. bolus or 0.4 micrograms/kg x hr i.v. infusion). We used a new fibrin monomer (FM) assay to follow the course of DIC. FM were detected by their ability to stimulate the tissue-type (t-PA) plasminogen activator dependent conversion of plasminogen to plasmin by a chromogenic assay. Miniplasminogen was used instead of plasminogen to avoid interference of the assay by alpha 2-antiplasmin. As a marker of DIC, elevated levels of FM were observed with all DIC-inducing agents (plasma levels were up to 90 micrograms/ml). The kinetics of FM formation were similar to the course of thrombin-antithrombin III (TAT) levels (maximal plasma levels 70 ng/ml); however, in the bacterial infection group, both parameters rose after a lag phase of about 1 hr. A 4 hr infusion of the highly specific thrombin inhibitor recombinant (rec.) hirudin (0.125 mg/kg x hr) resulted in a decrease of FM levels from 89.2 +/- 14.4 micrograms/ml in the LPS group (n = 10) to 27.4 +/- 11.2 micrograms/ml in the rec. hirudin group (n = 10; P < 0.001). The respective values for TAT levels were 73.1 +/- 19.7 micrograms/ml in the LPS group and 52.7 +/- 15.7 ng/ml in the rec. hirudin group (P < 0.001). Other coagulation parameters, such as platelets, fibrinogen, and fibrin(ogen) degradation products, were ameliorated accordingly.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Formation of fibrin monomers in experimental disseminated intravascular coagulation and its inhibition by recombinant hirudin. 805 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>