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)

Whilst increased plasma beta-thromboglobulin (beta TG), platelet factor 4 and thrombospondin levels are regarded as reflecting the release reaction of platelets, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) levels represent endothelial release reaction and/or damage. In this study including 12 smokers and 9 nonsmokers, we investigated the acute and chronic effect of smoking on these parameters and antithrombin III, protein S and fibrinogen, as well. Nonsmokers were found to have somewhat higher plasma levels of beta TG, t-PA and PAI-1 than chronic smokers, and 30 minutes after smoking two cigarettes, these levels and protein S levels of nonsmokers showed more prominent increases than of chronic smokers. It is speculated that chronic exposure to cigarette smoke may cause "exhaustion" or "receptor down-regulation" of platelets and endothelial cells, resulting with diminished release reaction of platelets and endothelium in response to acute smoking.
 ...
PMID:The acute effect of smoking on platelet and endothelial release reaction is suppressed in chronic smokers. 153 35

Cytosols of malignant breast tissue contained significantly higher levels of thrombospondin (TSP) and von Willebrand factor (vWF) than non-malignant breast. TSP and vWF content of human breast were significantly correlated whereas there was no correlation between TSP and the platelet-specific protein beta-thromboglobulin (beta TG). Whilst TSP in pre-menopausal breast cancer was slightly lower than in post-menopausal breast cancer, it did not correlate with oestrogen receptors (ER) or progesterone receptors (PR), but was negatively correlated with tissue-type plasminogen activator (tPA), an oestradiol-inducible enzyme. Secretion of TSP by MCF-7 cells was low and refractory to hormones. High levels of TSP appeared to be associated with the centre of the tumour mass. It is suggested that activation of the endothelium may be responsible, at least in part, for the high levels of TSP found in malignant breast tissue and could be a factor in the growth and spread of breast cancer.
 ...
PMID:Thrombospondin in malignant and non-malignant breast tissue. 252 76

The discovery of a fast-acting plasminogen activator inhibitor has resulted in the notion that the balance between tissue-type plasminogen activator and its inhibitor determines the net fibrinolytic activity of blood. The inhibitor shows a rapidly fluctuating acute-phase pattern, which may be important in relation to thrombosis in acute disease. Other newly discovered modulators of the fibrinolytic system include histidine-rich glycoprotein, tetranectin and thrombospondin. The role of fibrin as a cofactor in its own dissolution is further elucidated with emphasis on local aspects. Therapeutic inhibition of overactive fibrinolysis by various drugs needs careful monitoring. Prophylactic stimulation of fibrinolysis is possible, e.g. by stanozolol or other drugs that lower inhibitor levels, but its proven value is as yet limited. Results of clinical trials with activators of the fibrinolytic system as thrombolytic agents are discussed in relation to the physiology of the fibrinolytic system.
 ...
PMID:Advances in clinical fibrinolysis. 294 32

Cell lines derived from 3 different types of human tumor (e.g., squamous carcinomas, melanomas and gliomas) were examined for production of plasminogen activator activity and for attachment and spreading on various extracellular matrix components in the presence or absence of plasminogen. All of the squamous carcinoma and melanoma lines produced high levels of plasminogen activator activity. In contrast, 4 of 6 glioma lines had undetectable activity. Cells from all 3 tumor types attached and spread on fibrinogen-coated or fibrin-coated plastic dishes in the absence of plasminogen. In the presence of exogenous plasminogen, the attachment and spreading of the cells which produced high levels of plasminogen activator activity was inhibited. The plasminogen activator-deficient cells were much less sensitive to exogenous plasminogen. In the presence of plasminogen, attachment and spreading on fibronectin-coated dishes was also partially inhibited. In contrast, plasminogen had no effect on the attachment and spreading of the cells on type-I or -IV collagen, laminin or thrombospondin. Previous studies have shown that tumor-cell adhesion to the extracellular matrix depends on the synthesis of receptors for extracellular matrix components or on the synthesis of extracellular matrix components themselves. The present study shows that, in addition, the production of enzymes which are capable of degrading these components also influences tumor-cell adhesion to extracellular matrix moieties.
 ...
PMID:Plasminogen activator production by human tumor cells: effect on tumor cell-extracellular matrix interactions. 369 23

In a group of six normal male volunteers, infusion of DDAVP, venous occlusion and exercise were shown to increase plasma levels of factor VIII and plasminogen activator, activity and antigen, to different extents and at differing rates. Any mechanisms suggested to explain release of these proteins by various stimuli should account for such differences. All three stimuli could also increase plasma levels of prostacyclin metabolites, although this was only significant for high doses of DDAVP. Other potential endothelial markers, such as fibronectin and thrombospondin, showed no specific increase after any of the stimuli.
 ...
PMID:A comparative study using immunological and biological assay of the haemostatic responses to DDAVP infusion venous occlusion and exercise in normal men. 642 76

The effects of hyperthermia on potentially prothrombotic endothelial function were investigated by measuring levels of von Willebrand factor, thrombospondin, tissue plasminogen activator and plasminogen activator inhibitor-1 secreted by unstimulated human umbilical vein endothelial cells cultured at 37 degrees C, 39 degrees C, 41 degrees C and 43 degrees C for 24 h. Endothelial barrier function at 43 degrees C was compared with that at 37 degrees C by measuring permeability to radiolabelled human serum albumin and low density lipoprotein. Thrombospondin levels were unaffected by a temperature of 39 degrees C; they increased after 3 h at 41 degrees C and subsequently declined to values significantly below the 37 degrees C control. At 43 degrees C, secretion exhibited a time-dependent decrease. Secretion of von Willebrand factor was not discernibly affected by exposure to 39 degrees C or 41 degrees C. Its response to 43 degrees C resembled that of thrombospondin to 41 degrees C. In contrast, elevated temperatures markedly increased plasminogen activator inhibitor-1 while decreasing t-PA secretion, though after prolonged exposure to 43 degrees C the levels of both returned to control values. After 12-24 h at 43 degrees C, endothelial permeability to both albumin and low density lipoprotein increased markedly. Vascular endothelium may contribute to the thrombotic tendency associated with heat stroke by increasing access to the prothrombotic subendothelium and reducing fibrinolysis.
 ...
PMID:The effects of hyperthermia on human endothelial monolayers: modulation of thrombotic potential and permeability. 805 50

Glucocorticoids reduce prostaglandin synthesis in cultured vascular endothelium, but their effects on other haemostatic functions are unclear. We examined the effects of dexamethasone and cyclosporin A (CSA) on cultured human umbilical vein endothelial cells (HUVEC). One, 10 and 50 micrograms/ml CSA and 1 microgram/ml dexamethasone (Dx) were added to the culture medium for 3 h, 3 days and 6 days and compared with HUVEC cultured in medium and serum alone. After assay of accumulated release of tissue type plasminogen activator (t-PA) and endothelin 1 (ET), cells were stimulated with 1 U/ml of human thrombin for 1 h and medium collected for RIA of 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), thrombospondin (TSP), von Willebrand factor (vWf) and ELISA of plasminogen activator inhibitor 1 (PAI-1). CSA at 1 microgram/ml modestly reduced release of prostacyclin (PGI2) but had no reproducible effects on other metabolites. CSA at 10 and 50 micrograms/ml inhibited cell growth and thrombin stimulated release of PGI2 in a time- and dose-dependent manner. Inhibition of other endothelial metabolites was also observed at CSA 10 > micrograms/ml. Dexamethasone 1 microgram/ml reduced both cell number and PGI2 release and increased thrombin stimulated release of vWf, TSP and PAI-1 with increases in t-PA and endothelin 1 in the medium. CSA 1 microgram/ml and dexamethasone 1 microgram/ml together were additive in reducing PGI2 release and increasing PAI-1 secretion. These observations suggest a role for endothelial dysfunction in the hypertensive and thrombotic complications observed in steroid treated patients with CSA potentially contributing to such complications.
 ...
PMID:Effects of cyclosporin A and dexamethasone on haemostatic and vasoactive functions of vascular endothelial cells. 858 11

Vascular endothelium is involved in both active and passive processes in haemostasis, but inflammatory cytokines such as interleukin 1 (IL-1) and tumour necrosis factor (TNF) have been reported to convert the comparatively inert endothelial cell to an inflammatory state. Acidic fibroblast growth factor (aFGF) in the presence of heparin has effects opposite to IL-1 on cultured human umbilical vein endothelial cells (HUVEC); therefore, we have investigated the modulation of IL-1-induced effects by the c combination of aFGF and heparin (aFGF/heparin). First passage HUVEC were cultured for 6 days in the presence of 20% human serum with and without the addition of 625 pM human recombinant aFGF (hr aFGF) and 7 microM heparin. On day 5, recombinant IL-1 beta was included for 24 h. The following day the cells were washed and measurements made of the release of prostacyclin, von Willebrand factor, plasminogen activator inhibitor type 1, and thrombospondin, both in the resting state and following stimulation for 60 min with 1 U/ml thrombin. Tissue-type plasminogen activator was assayed in HUVEC lysates. Similar experiments were performed to assess effects on the expression of vascular adhesion molecule, intracellular adhesion molecule, and E-selectin using an ELISA on cells in situ. This study indicates that aFGF/heparin in the culture medium of HUVEC abrogates the measured responses to IL-1. These data imply that routine endothelial cell culture with aFGF/heparin may cause artefacts, the effects of FGF and Il-1 may involve common pathways, and FGF/heparin may offer an approach to design therapeutics to counter the adverse effects of IL-1.
 ...
PMID:Fibroblast growth factor and heparin protect endothelial cells from the effects of interleukin 1. 861 63

Acidic and basic fibroblast growth factor (aFGF and bFGF respectively) are closely related mitogens (55% homology) of the heparin binding growth factor family. Reports of the relative potency of these growth factors and the ability of heparin to potentiate the activity of bFGF are conflicting. We have examined the effect of heparin and human recombinant aFGF and bFGF on basal and thrombin challenged release of metabolites from cultured human umbilical vein endothelial cells (HUVEC). Culture supernatant was assayed for thrombospondin, prostacyclin and PAI-1 and cell lysates were analysed for t-PA. aFGF and bFGF were equipotent in regulating ther release of all metabolites studied, except thrombin stimulated release of PGI2 where bFGF was more potent than aFGF in the absence of heparin. Heparin potentiated the mitogenic and metabolic effects of both bFGF and aFGF. However, heparin was not essential for the expression of the biological activity of FGF.
 ...
PMID:Acidic and basic fibroblast growth factors have comparable effects on the haemostatic function of vascular endothelium. 867 45

In addition to autoregulating its own expression, transforming growth factor-beta 1 (TGF-beta1) also regulates the production of proteases, protease inhibitors and extracellular matrix proteins. To investigate the relationship between plasminogen activator (PA), plasminogen activator inhibitor-1 (PAI-1) and the extracellular matrix in malignant and normal lung epithelial cells and to determine whether malignant lung epithelial cells may be more invasive than normal lung epithelial cells because of differences in expression of these proteins in response to TGF-beta, the regulation of PA, PAI-1, fibronectin, laminin and thrombospondin by TGF-beta1 in human non-small cell lung cancer (NSCLC) cells was examined and compared with normal human bronchial epithelial (NHBE) cells. TGF-beta1 caused a persistent increase in expression of the mRNAs for both PA and PAI-1 in NSCLC cells, with the increase in PAI-1 mRNA beginning several hours before that of PA mRNA. By immunoprecipitation analysis, it was shown that TGF-beta1 also induced a corresponding increase in the amount of PAI-1 protein in these NSCLC cells as well. In contrast, while TGF-beta1 also increased expression of PAI-1 mRNA in NHBE cells, expression of PA mRNA decreased simultaneously. Treatment of NSCLC cells with TGF-beta1 resulted in a persistent increase in expression of the mRNAs for fibronectin, laminin and thrombospondin; expression of fibronectin protein also increased after treatment with TGF-beta1 in these cells. When NHBE cells were similarly cultured in the presence of TGF-beta1, expression of fibronectin mRNA also increased in a persistent manner; however, only an early transient increase in the level of the mRNAs for laminin and thrombospondin was detected in these cells. These data show that there is differential regulation of the genes for PA and PAI-1 and the extracellular matrix protein fibronectin in response to TGF-beta1 not only when NSCLC and NHBE cells are compared, but also when different NSCLC cells are compared with each other.
 ...
PMID:Differential regulation of protease and extracellular matrix protein expression by transforming growth factor-beta 1 in non-small cell lung cancer cells and normal human bronchial epithelial cells. 929 10


1 2 3 4 Next >>