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

The effects of contraceptive steroids on the expression of endothelial homeostasis were examined by direct and indirect measures in women with insulin-dependent diabetes mellitus (IDDM) in a prospective nonrandomized controlled study. Study subjects were 13 women with uncomplicated IDDM treated with a monophasic combination of 30 micrograms ethinyl estradiol and 75 micrograms gestodene for 12 consecutive cycles and 13 women of comparable diabetic status as control. During the study period, none of the participants developed increased renal albumin excretion, which was used as a direct measure of endothelial function. In the indirect assessment of endothelial function, we found a proportionate increase in plasma levels of thrombin-antithrombin III (TAT) complexes and D-dimer during treatment. Hormonal intake was followed by decreased antigen concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (type 1 [PAI-1]), whereas the activities of t-PA and PAI-1 were unchanged. Plasma levels of plasminogen and histidine-rich glycoprotein (HRG) increased and decreased, respectively, whereas an increase in von Willebrand factor was observed in the treatment group. No significant changes in direct or indirect measures were observed in the control group during the observation period of 12 months. In conclusion, no adverse effect on endothelial function was demonstrated by direct measures, but our findings suggest that a procoagulant state, compensated by enhanced activity of the fibrinolytic system, is induced by hormonal treatment. Clinical and metabolic monitoring is recommended if the use of oral contraceptives in women with IDDM is extended.
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PMID:Assessment of endothelial function during oral contraception in women with insulin-dependent diabetes mellitus. 796 93

Fibrinolytic parameters and von Willebrand factor (vWF) antigen were measured in the plasma of 10 patients with hemolytic uremic syndrome (HUS). Samples were taken at presentation and again 2 wk later, before and after infusion of 1-desamino-8-arginine vasopressin. Compared with the plasma values of healthy control children, levels of tissue-plasminogen activator (t-PA) antigen, plasminogen activator inhibitor type I (PAI-1) activity, and vWF as well as fibrin(ogen) degradation products were significantly elevated in the plasma of HUS patients on admission. No response of the fibrinolytic parameters and vWF were seen when 1-desamino-8-arginine vasopressin infusion was given on admission. After 2 wk, t-PA antigen and vWF had partially returned to basal values, and t-PA antigen increased rapidly again after 1-desamino-8-arginine vasopressin infusion. To investigate whether verocytotoxin contributes to the alteration of the fibrinolytic system found in HUS patients, purified verocytotoxin-1 (VT-1) was added to the media of cultured human endothelial cells. Addition of VT-1 alone did not change the production of t-PA, plasminogen activator inhibitor type I, and vWF antigen in these cells. However, when the endothelial cells were preincubated with tumor necrosis factor-alpha to increase the number of VT-1 receptors, VT-1 induced a marked decrease of the synthesis of t-PA, plasminogen activator inhibitor type I, and vWF. This was caused by a decrease in overall protein synthesis in the tumor necrosis factor-alpha- and VT-1-treated endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The fibrinolytic system in the hemolytic uremic syndrome: in vivo and in vitro studies. 797 Sep 42

Tumor necrosis factor alpha (TNF-alpha) is a cytokine that affects endothelial cells' function by changing their antithrombotic potential to a net procoagulant effect. Only a few data have so far been reported for the pathophysiologic role of TNF in vascular diseases in the involvement of microvessels and/or macrovessels and a prothrombotic state. In the present study the authors evaluated plasma TNF (and interleukin-1) levels in 20 patients with chronic arterial obstructive disease (CAOD) with intermittent claudication and 10 CAOD patients with more severe disease (pain at rest/skin ulcers). In addition, they studied 10 patients with Raynaud's phenomenon (RP), suspected to be secondary to a collagen disease. The control group consisted of 20 subjects matched for sex and age with the three groups of patients. TNF levels were assayed by enzyme-linked immunosorbent assay. The antigen levels of von Willebrand factor (vWF), tissue plasminogen activator (t-PA), and its inhibitor (PAI) were also determined as markers of release from the endothelium, while the fragment 1 + 2 of prothrombin (F1 + 2) and thrombin-antithrombin III (TAT) complexes were assessed as indexes of systemic thrombin generation. TNF levels were significantly higher in both groups of CAOD patients than in controls or RP patients, and the same was true for vWF. t-PA was significantly higher only in the CAOD subjects with more severe disease. No differences among groups were seen in PAI antigen/activity or thrombin generation. When data were corrected for age, TNF no longer differentiated CAOD patients from controls and RP subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma levels of tumor necrosis factor and endothelial response in patients with chronic arterial obstructive disease or Raynaud's phenomenon. 798 28

The aim of this study was to compare the secretory response of the vascular wall in vivo to DDAVP (i.v. 0.3 microgram/kg, 30 min) and to venous occlusion (VO, 20 min) in control healthy subjects, patients with von Willebrand's disease type I (vWd I) and patients with von Willebrand's disease type III (vWd III). In controls (n = 10) and vWd I (n = 12), DDAVP induced a 2 to 3-fold rise in plasma von Willebrand factor antigen (vWf: Ag), factor VIII coagulant activity (VIII: C) and tissue--type plasminogen activator antigen (t-PA:Ag). VO was less effective in increasing vWf: Ag and VIII:C but produced a greater rise in t-PA:Ag. Large increments (over 10-fold) were observed in plasmin-alpha 2-antiplasmin complexes following both stimuli. In vWd III (n = 10), DDAVP and VO failed to increase vWf:Ag, VIII:C and t-PA:Ag. No significant changes in plasmin-alpha 2-antiplasmin complexes were observed in this group. Moreover, the baseline t-PA:Ag values were significantly lower in vWd III (2.17 +/- 1.13 ng/ml) than in controls (4.84 +/- 1.97 ng/ml, p < 0.001). A significant increase in urokinase--type plasminogen activator antigen (u-PA:Ag) was found only in controls after VO. Neither controls nor patients with vWd showed any changes in plasma fibronectin levels following DDAVP. The low t-PA:Ag results and the abnormal fibrinolytic response to DDAVP and VO in patients with severe (type III) vWd indicate that their endothelial cell abnormality is more extensive than the defect in the synthesis or release of vWf.
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PMID:Secretory response of the vessel wall to DDAVP and venous occlusion in von Willebrand's disease. 799 99

Due to the incidence of symptomatic atherosclerosis in uremic patients, hemostasis-derived cardiovascular risk factors, basal plasma concentrations of some endothelial-derived glycoproteins and desmopressin-induced variations of endothelial-derived proteins were studied in 22 uremic patients on prolonged maintenance hemodialysis with no cardiovascular antecedent. Compared to control subjects, patients had increased predialysis hemostasis-related cardiovascular risk factors: high fibrinogen, proconvertin, and type 1 plasminogen activator inhibitor plasma concentrations; low albumin values; generally low antithrombin III values but sometimes high. They had high predialysis plasma concentrations of endothelium-derived glycoproteins: von Willebrand factor, tissue-type plasminogen activator and urokinase-type plasminogen activator, which are secreted by endothelial cells, but also soluble thrombomodulin, a marker of endothelial cell injury. The desmopressin-induced release of tissue-type plasminogen activator and of von Willebrand factor were lower than in controls. High fibrinogen, type 1 plasminogen activator inhibitor and low albumin plasma concentrations may be linked to repeated acute phase reactions associated with hemodialysis. Data concerning endothelium-related proteins are concordant with the co-existence of a chronic in vivo endothelial activation and endothelial injury in uremia. This could be linked to the initiation and progression of atherosclerosis.
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PMID:Increased cardiovascular risk factors and features of endothelial activation and dysfunction in dialyzed uremic patients. 799 2

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).
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PMID:The control of production and release of haemostatic factors in the endothelial cell. 802 46

The aims of this study were to determine whether elevated plasminogen activator inhibitor type 1 (PAI-1) activity after myocardial infarction reflects baseline PAI-1 or represents an acute-phase response secondary to the infarction, and to determine how tissue plasminogen activator (t-PA) activity and total t-PA antigen levels in healthy control subjects differ from those in patients after myocardial infarction. Compared with healthy control subjects, patients studied 1-3 months after infarction had elevated levels of PAI-1 activity and fibrinogen but normal levels of C-reactive protein and von Willebrand factor antigen, whereas patients with a noncardiac acute-phase response showed elevation of all four proteins. Elevated PAI-1 activity in the absence of elevations in other acute-phase proteins suggests an intrinsic increase in PAI-1 secretion in the post-myocardial infarction group. In addition, when compared with healthy control subjects, post-myocardial infarction patients had higher levels of total t-PA antigen (bound and free t-PA) but lower t-PA activity and a lower percentage of active t-PA. Overall, survivors of myocardial infarction have reduced t-PA activity and increased PAI-1 activity that is not due to a prolonged acute-phase response.
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PMID:Laboratory evaluation of fibrinolysis in patients with a history of myocardial infarction. 804 97

In recent years, it is known that endothelial cells play an important role in the genesis of some diseases, but there are only few papers dealing with the role of endothelial cells in leukemia. In this study some of the active factors released by the endothelial cells in patients with acute leukemia such as von Willebrand factor, prostaglandin, fibronectin, tissue-type plasminogen activator and its inhibitor were determined. It was found that the levels of these factors changed significantly in patients with acute leukemia, as compared with those in normal controls, especially in cases with bleeding tendency and infection. The possible mechanism and the clinical significance were discussed.
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PMID:[Active factors released by endothelial cells in acute leukemia]. 804 83

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.
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PMID:The effects of hyperthermia on human endothelial monolayers: modulation of thrombotic potential and permeability. 805 50

Some well-described similarities exist between tissue plasminogen activator (t-PA) and von Willebrand factor (vWf) which may suggest a link in either the synthesis or release of both proteins from endothelial cells. To investigate this relationship further immunocytochemical localization of t-PA and vWf was performed in normal tissues and in skin obtained from patients with type I and type III von Willebrand's disease (vWd). Components of the fibrinolytic system were measured at baseline and after venous occlusion in healthy controls and patients with vWd. Patients with severe vWd received intravenous vWf concentrate, followed by desmopressin (DDAVP), to study the plasma response of vWf and t-PA. By immunocytochemical staining, t-PA was demonstrated in endothelial cells of normal skin, kidney and liver and also in the skin of patients with type I and type III vWd. vWf was localized in endothelial cells of all tissues except the specimens from an individual with severe vWd. Basal plasma levels of fibrinolytic components were normal in patients with vWd. Venous occlusion resulted in a rise of fibrinolytic activity in controls and patients with type I, but not type III, vWd. No rise in plasma t-PA was observed following DDAVP in severe vWd, even though near-normalization of plasma vWf levels had been obtained by prior infusion of vWf concentrate. It is concluded that the synthesis of t-PA and vWf is probably regulated by independent processes. Constitutive and regulated release of both proteins occur through different mechanisms and the basal secretion of t-PA is intact in severe vWd.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Study of endothelial t-PA and vWf in normal subjects and in von Willebrand's disease. 807 4


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