Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urinary kallikrein and kallikrein activity significantly decreased in cases of preeclampsia (u-kall./CRE.index 42.39 +/- 9.66 ng/mg, u-kall. act./CRE.index 0.26 +/- 0.06 ng/min/mg), and urinary kininase II and kininase activity significantly increased (u-kininase/CRE.index 10.91 +/- 1.26 x 10(-3) IU/min/mg, u-kininase act./CRE.index 506.37 +/- 178.45 pg/min/mg) when compared with those of normal gravidas from 28 weeks to 42 weeks of gestation (u-kall./CRE.index 189.31 +/- 14.17 ng/mg, u-kall. act./CRE index 1.08 +/- 0.10 ng/min/mg, u-kininase/CRE.index 6.24 +/- 0.31 x 10(-3) IU/min/mg, u-kininase act./CRE.index 15.64 +/- 0.10 pg/min/mg). Urinary FPA, B beta 5-42, alpha 2-PI, and alpha 2PI-plasmin-complex (PIC) significantly increased in preeclampsia (u-FPA/CRE.index 23.59 +/- 8.47 ng/mg, u-B beta/CRE.index 105.26 +/- 29.30 ng/mg, u-alpha 2PI/CRE.index 121.53 +/- 43.57 ng/mg, u-PIC/CRE index 278.39 +/- 60.50 ng/mg) when compared with those of normal control group (u-FPA/CRE.index 0.92 +/- 0.04 ng/mg, u-B beta/CRE.index 12.15 +/- 0.44 ng/mg, u-alpha 2PI/CRE.index 4.18 +/- 0.33 ng/mg, u-PIC/CRE.index 5.98 +/- 1.15 ng/mg). Urinary urokinase markedly increased and urinary D-dimer was detected in severe cases of preeclampsia (u-UK/CRE.index 58.20 +/- 43.69 ng/mg, u-D-dimer 54.76 +/- 9.89 ng/ml) when compared with those of normal control group. These findings suggest that deficiency in urinary kinin excretion may induce hypertension in addition to the changes of urinary coagulation-fibrinolysis system that represents the occurrence of either the endothelial cell injury in the glomerulus or the renal tulbular damage in mild cases of preeclampsia, eventually resulting in the intra-renal vascular coagulation.
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PMID:Urinary coagulation-fibrinolysis, kallirein-kinin systems and kininase in cases of preclampsia. 133 34

A method is described for distinguishing coagulation from fibrinolysis by three estimates of fibrinogen. This "fibrinogen series" together with plasma antithrombin and urinary urokinase have been compared in pregnant patients with venous thrombosis and pre-eclampsia. Evidence is presented for active coagulation during deterioration of the pre-eclampsia state and for enhanced fibrinolysis during improvement.
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PMID:Assessment of coagulation and fibrinolysis in pre-eclampsia. 459 83

Plasma fibrinolytic activity and plasma inhibitory activity against urokinase and tissue activator were measured in primigravidae with moderate or severe pre-eclampsia and in gestation-matched primigravidae with uncomplicated pregnancy. The mean levels of fibrinolytic activity and inhibitory activity against urokinase and tissue activator did not differ significantly between the pre-eclampsia and uncomplicated pregnancy groups. The pattern of inhibitory fractions of plasminogen-depleted plasma from pre-eclamptic and uncomplicated primigravidae after gel filtration on sephadex G-100 was similar.
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PMID:The fibrinolytic system in pre-eclampsia. 642 99

The objectives of this study were (1) To assess human umbilical cord vein endothelial cell (HUVEC) fibronectin (Fn) content and integrity in patients with preeclampsia and (2) to investigate the ability of Fn and Fn fragments (FnDP) to disrupt endothelial cell attachment to an Fn matrix through modulation of plasminogen activator activity. Intact Fn was released from normal cord veins, while Fn and FnDP (70 and 21 kd) were released from cord veins in culture from patients with severe preeclampsia. Factor VIII and Fn immunostaining of normal cord sections revealed endothelial integrity and low Fn content, while immunostaining of cord sections from patients with preeclampsia revealed a disrupted endothelium and high concentrations of Fn. Both intact Fn and FnDP isolated from patient plasma or prepared by plasmin digestion of pure Fn had no effect on chromium 51 release from HUVECs. These FnDP, but not intact Fn, stimulated HUVEC urokinase plasminogen activator production within 2 hours (p < 0.05) and caused a time- and concentration-dependent detachment and disruption of the HUVEC monolayers and HUVEC-mediated degradation of immobilized iodine 125-labeled Fn underneath the HUVEC monolayer (p < 0.02) after 2 hours. This 125I-labeled Fn release was enhanced by plasminogen and inhibited by aprotinin. Thus FnDP appear to cause endothelial cell disruption that may be due to plasmin generation in vitro.
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PMID:Degradation of fibronectin in association with vascular endothelial disruption in preeclampsia. 770 9

Urokinase (u-PA) dissolves and removes fibrin deposits in the renal secretory pathways in various renal diseases. During pregnancy nephropathy creates a problem in preeclampsia and diabetes, but the underlying mechanism of glomerular damage is different. Preeclamptic nephropathy is characterized as 'glomerular endotheliosis' with hypertrophy of the intracapillary cells, and diabetic nephropathy as 'glomerulosclerosis' with hyaline deposits. The role of fibrin deposition for the etiology of renal damage in preeclampsia is controversial. Changes of the urinary secretion of u-PA may reflect the type of glomerular damage. Our hypotheses were that renal insufficiency is associated with a low u-PA activity in both conditions, and that severe disease is parallel to declining concentrations of u-PA. We compared the glomerular filtration rate, S-Creatinine and S-Urate with urinary u-PA excretion in 24 hypertensive and 20 diabetic pregnant women. In diabetic patients, a low u-PA concentrations was associated with an impaired renal function. In hypertensive pregnancy, the u-PA excretion did not reflect the severity of the hypertensive disease or renal function. No association was found between u-PA excretion and renal function post partum in any group. We conclude that renal urokinase activity plays a role for renal function in diabetic but not in hypertensive pregnancy.
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PMID:Renal function and urinary urokinase in hypertensive and diabetic pregnancies. 782 57

In pre-eclampsia (PE), reduced levels of plasma urokinase-like plasminogen activator (u-PA) and plasminogen activator inhibitor-2 (PAI-2), and increased levels of plasma tissue-type plasminogen activator (t-PA) antigen were seen. The majority of moderate and severe pre-eclamptic women (7 out of 10) ended up with pre-term delivery as compared with 2 out of 11 who went on to term. Patients with moderate and severe PE had significantly lower levels (mean +/- SD, ng/ml) of PAI-2 (58.4 +/- 34.9) and u-PA antigen (1.61 +/- 0.62) as compared to those with mild PE (95.6 +/- 39.3 and 1.61 +/- 0.62 and 2.12 +/- 0.61, respectively). Significantly raised t-PA antigen (14.6 +/- 5.7 ng/ml) was seen in moderate and severe PE as compared with mild PE (9.9 +/- 3.4 ng/ml). PAI-1 activity was significantly raised only in moderate and severe PE as compared with normal pregnancy. There were no significant differences in thrombin-antithrombin-III complexes, D-dimer and beta-thromboglobulin levels between the PE group and normal pregnancy, although these parameters were above the non-pregnant levels. Platelets in PE were within the range found in normal pregnancy. It appears that measurements of plasma u-PA and PAI-2 levels in patients with PE may have prognostic value in determining the outcome of pregnancy in this pregnancy disorder.
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PMID:Plasminogen activators, plasminogen activator inhibitors and markers of intravascular coagulation in pre-eclampsia. 833 Jul 65

We previously reported significantly elevated levels of plasminogen activator inhibitor type 1 (PAI-1) in plasma and placenta from pregnant women with severe pre-eclampsia, and pre-eclampsia is a frequent problem in molar pregnancies. As increases in PAI-1 may contribute to the placental alterations that occur in pre-eclampsia, we have begun to investigate changes in PAI-1 as well as PAI-2 and several other components of the fibrinolytic system in patients with trophoblastic disease. Significant increases in plasma PAI-1 and decreases in plasma PAI-2 levels were observed in molar pregnancies when compared with the levels in normal pregnant women of similar gestational age. PAI-1 antigen levels also were increased, and PAI-2 levels were decreased in placenta from women with molar pregnancies compared with placenta obtained by spontaneous abortion. Immunohistochemical analysis revealed strong positive and specific staining of PAI-1 in trophoblastic epithelium in molar pregnancies and relatively weak staining of PAI-2. No association between the distribution of PAI-1 and vitronectin was found, and no specific signal for tissue type PA, urokinase type PA, tumor necrosis factor-alpha, or interleukin-1 was detected. In situ hybridization revealed an increase in PAI-1 but not PAI-2 mRNAs in placenta from molar pregnancies in comparison with placenta from abortions. These results demonstrate increased PAI-1 protein and mRNA in trophoblastic disease and suggest that localized elevated levels of PAI-1 may contribute to the hemostatic problems associated with this disorder.
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PMID:Abnormal expression of plasminogen activator inhibitors in patients with gestational trophoblastic disease. 886 72

The antigen levels of plasminogen activator inhibitor type 1 (PAI-1), plasminogen activator inhibitor type 2 (PAI-2), tissue-type plasminogen activator (t-PA), and urokinase-type plasminogen activator (u-PA) were measured during pregnancy and severe preeclampsia. The PAI-1 and PAI-2 antigen levels increased linearly during pregnancy and promptly returned to the level of non-pregnant women after delivery. The t-PA and u-PA antigen levels increased slowly and linearly during pregnancy. In severe preeclampsia, the PAI-2 antigen level was lower than that observed during the 3rd trimester of normal pregnancy, and the t-PA antigen level was higher than that during the 3rd trimester of normal pregnancy. Immunohistochemical examination of placental tissue showed that the PAI-2 and u-PA antigens were localized in syncytiotrophoblasts. In severe preeclampsia, the PAI-2 and u-PA antigens in placental tissue did not stain as clearly as during the 3rd trimester of normal pregnancy. The PAI-2 and u-PA antigen levels showed a positive correlation with birth weight. Therefore, PAI-2 may be an important marker of placental function and abnormality in pregnancies.
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PMID:Fibrinolysis during normal pregnancy and severe preeclampsia relationships between plasma levels of plasminogen activators and inhibitors. 887 12

Marked changes in the hemostasis system, especially increases in PAI-2, are observed during pregnancy and at delivery. This inhibitor is produced by placental trophoblasts and by macrophages. PAI-2 occurs in two forms, a LMW and a HMW form. LMW PAI-2 is intracellular, HMW PAI-2 is secreted. PAI-2 inhibits both u-PA and two-chain t-PA. PAI-2 seems to be involved in the processes of invasion and remodeling of fetal and uterine tissues. It may protect against premature placental separation and secure hemostasis at parturition. Excess levels of PAI-2 in amniotic fluid may protect membranes from premature rupture. An imbalance between fibrinolytic activators and inhibitors may also be related to intracranial hemorrhage in premature infants. During preeclampsia t-PA and PAI-1 levels are markedly increased in plasma, and in cases of intrauterine growth retardation, u-PA and PAI-2 levels are decreased. While elevated PAI-1 concentrations might be helpful markers of severity of preeclampsia, decreased PAI-2 levels seem to indicate decreased placental function and intrauterine growth retardation.
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PMID:Significance of the plasminogen activator inhibitor of placental type (PAI-2) in pregnancy. 983 9

Although progress has been made toward our understanding of the pathophysiology of pre-eclampsia, the precise aetiology of this disease still remains an enigma. One of the hallmarks of pre-eclampsia is a failure of the extravillous cytotrophoblast cells to invade and remodel the uterine spiral arterioles during the first trimester of pregnancy. Moreover, studies suggest that the cause of this disorder may be immunological in nature. Evidence is provided here suggesting that impaired trophoblastic invasion of the spiral arterioles may be linked to the altered immunological response associated with pre-eclampsia. Previous studies by Reister et al., 1999 demonstrated a direct relationship between macrophage infiltration of the myometrial segments of spiral arterioles and reduced trophoblastic invasion in pre-eclampsia. Also, it is well established that activated macrophages produce large amounts of nitric oxide (NO). Our present findings reveal that low concentrations of NO-mimetic drugs (glyceryl trinitrate and sodium nitroprusside) inhibit the ability of trophoblast cells to penetrate through reconstituted extracellular matrix (Matrigel). This inhibition is accompanied by a reduced expression of the cell surface urokinase receptor, a molecule important for invasion. These results suggest a possible mechanistic link between the aberrant macrophage infiltration associated with pre-eclampsia, and the maladapted uteroplacental arterioles that characterize the disease.
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PMID:Does nitric oxide play a role in the aetiology of pre-eclampsia? 1131 29


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