Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial cell damage in systemic lupus erythematosus (SLE) was evaluated by measuring fibrinolytic activity and von Willebrand factor levels. Tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) activity, and von Willebrand factor antigen (vWF:Ag) and activity (vWF:RCof) were measured in 21 SLE patients (12 of whom were therapy free) and 22 controls. In addition, the relationship between such parameters and Raynaud's phenomenon, disease activity [according to personal criteria, Systemic Lupus Activity Measure (SLAM) and European Consensus Lupus Activity Measurement (ECLAM) scores] inflammatory indices [ESR, C-reactive protein (CRP), alpha 2-globulin], anticardiolipin antibodies and corticosteroid therapy was investigated. Lower levels of t-PA antigen (P = 0.003) and higher levels of vWF:Ag (P = 0.001) were found in SLE patients in comparison with controls. Moreover, t-PA antigen was lower (P = 0.02) in steroid-free patients in comparison with those taking steroids. No relationship was found between fibrinolysis and coagulation abnormalities and Raynaud's phenomenon, disease activity, inflammatory indices and anticardiolipin antibodies. Endothelial cell damage is probably a common feature in SLE patients; nevertheless, we were unable to clarify the nature of such abnormality. It is worth noting that low doses of steroids seem to be effective in improving endothelial cell function in SLE patients.
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PMID:Fibrinolysis and coagulation abnormalities in systemic lupus erythematosus. Relationship with Raynaud's phenomenon, disease activity, inflammatory indices, anticardiolipin antibodies and corticosteroid therapy. 772 97

The cause of thrombosis in the antiphospholipid syndrome (APS) is unknown. There have been reports of abnormalities in the antigenic levels or activity of endothelium-derived haemostatic factors, such as tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1); however the data from these studies are conflicting. We studied plasma from nine patients with APS; seven of them had a history of thrombosis, and three had systemic lupus erythematosus (SLE). We also studied nine matched control patients who had SLE without APS, and 14 healthy individuals. We measured t-PA, von Willebrand factor (vWF), anticardiolipin antibody (ACA) and anti-endothelial cell antibody (AECA) levels by enzyme-linked immunoassay (ELISA), PAI-1 activity by a parabolic-rate chromogenic assay, and lupus anticoagulant (LA) activity by a standard mixing test. For t-PA and PAI-1, measurements were made on morning and evening plasma samples. The two groups of patients did not differ significantly with respect to age, sex, plasma lipids or anti-inflammatory drugs. Most APS patients (7/9) but none of the controls were taking warfarin. Between the APS and the control patients no significant differences were detected in t-PA, PAI-1, vWF or AECA levels. When APS patients were considered alone, vWF levels correlated positively with IgG ACA levels (r = 0.81, P < 0.01) and negatively with platelet count (r = -0.68, P < 0.05). There was no correlation between levels of ACA or LA activity and t-PA, PAI-1 or AECA. Compared with healthy volunteers, the diurnal variation of t-PA and PAI-1 was blunted in the two patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelium-derived haemostatic factors and the antiphospholipid syndrome. 772 92

Many renal diseases are associated with fibrin deposition in the glomeruli, a situation that reflects an abnormality in the balance between the coagulation and fibrinolytic systems. We recently demonstrated that normal mouse kidney contains very low levels of type 1 plasminogen activator inhibitor (PAI-1), a potent anti-fibrinolytic protein, but that during endotoxemia, large amounts of PAI-1 protein and mRNA are expressed in glomerular and peritubular endothelial cells. These results raise the possibility that overexpression of PAI-1 in the glomerulus may contribute to the ongoing pathology seen in renal disease. To directly investigate this possibility, we studied PAI-1 expression in MRL/lpr mice, using in situ hybridization and immunohistochemistry. Female MRL/lpr mice develop early onset lupus glomerulonephritis (GN), a disease in which fibrin deposition is detected in the glomerulus and in which anti-coagulation therapy improves the prognosis. We detected very low levels of PAI-1 mRNA and antigen in the smooth muscle cells of renal vessels and in the renal papilla of 16 control mice. In contrast, PAI-1 was expressed in relatively high levels throughout the kidneys of 33 out of 34 diseased mice, both within the glomerulus and also in tubules and vessels. Moreover, the level of PAI-1 in the tissues seemed to correlate with the severity of the disease. PAI-1 expression was localized to endothelial cells, parietal epithelial cells, tubular epithelial cells and infiltrating mononuclear cells in the tubulointerstitium. None of these cells express detectable levels of PAI-1 in the normal kidney. The inappropriate expression of PAI-1 in the kidneys of mice with lupus GN suggests that this important inhibitor of fibrinolysis may play a role in the pathogenesis of this disease process.
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PMID:Expression of type 1 plasminogen activator inhibitor in renal tissue in murine lupus nephritis. 773 Nov 40

Calorie restriction (CR) and/or reduced energy intake ameliorates the progression of autoimmune renal disease in (NZB x NZW)F1 (B/W) female mice and increases life span. Like other forms of glomerulonephritis, the lupus-like kidney disease observed in these animals is frequently accompanied by glomerular deposition of fibrin and increased accumulation of mesangial matrix. Because alterations in plasminogen activator inhibitor type 1 (PAI-1) expression or function may be involved in both fibrin deposition and accumulation of extracellular matrix, we have studied the effects of CR on the expression of PAI-1 in kidneys from female B/W mice fed either ad libitum or on a 40% CR diet. By immunohistochemistry and immunoblotting, we found that the glomerular levels of PAI-1 antigen were highest in older ad lib fed animals with more advanced glomerular disease. Increased levels of PAI-1 protein were paralleled by increased levels of PAI-1 mRNA in total RNA extracted from renal cortex and in diseased glomeruli as detected by in situ hybridization. CR diminished the accumulation of PAI-1 protein and reduced the expression of PAI-1 mRNA. Thus, glomeruli from animals fed ad lib showed much greater deposition of PAI-1 protein, increased expression of PAI-1 mRNA, and more severe histological abnormalities than animals on a CR diet. The differences between CR and ad lib animals were more pronounced in animals studied at 9 to 10 months versus those at 3 to 4 months of age. These observations indicate that the ameliorating effects of CR include diminished PAI-1 gene expression and decreased localization of PAI-1 in glomeruli.
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PMID:Effects of energy intake on type 1 plasminogen activator inhibitor levels in glomeruli of lupus-prone B/W mice. 785 20

Antiphospholipid syndrome is characterized by thrombosis, recurrent fetal loss, thrombocytopenia and is associated with the presence of antiphospholipid antibodies, especially anticardiolipin antibodies. We present a patient with the clinical features of antiphospholipid syndrome, namely recurrent venous and arterial thrombosis, recurrent abortions, thrombocytopenia and libido reticularis but with persistently negative serology for any type of antiphospholipid antibody. The possible existence of 'seronegative' antiphospholipid syndrome is proposed. Of additional interest in this patient is the presence of significantly elevated levels of plasminogen activator inhibitor. The role of this inhibitor, if any, in the antiphospholipid syndrome and/or seronegative antiphospholipid syndrome is not known and merits further study.
Lupus 1994 Jun
PMID:Seronegative antiphospholipid syndrome associated with plasminogen activator inhibitor. 795 6

Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are frequently detected in sera from patients affected by systemic lupus erythematosus (SLE). However, the role of antiphospholipid antibodies (aPL) in thrombus formation has not been defined as yet. Twenty-two patients affected by SLE, all fulfilling the 1982 ARA revised criteria, and twenty healthy subjects were investigated for the presence of LA, aCL and other aPLs. Monocyte procoagulant activity-PCA (Tissue Factor production) was evaluated by one stage plasma recalcification time. In all patients the plasma levels of F1 + 2 and of plasminogen activator inhibitor (PAI) were also determined. Monocyte PCA was significantly higher in SLE patients with LA and/or aCL in comparison to SLE patients without LA and/or aCL (p < 0.01) and to controls (p < 0.05). However, no connection was observed between PCA expression by mononuclear cells and LA or aCL levels. No differences in F1 + 2 and PAI plasma levels were found between SLE patients with or without aPL and controls. In our SLE patients LA and/or aCL positivity appears strictly related to an increased monocyte activation that could play an important role in the occurrence of thrombotic events.
Lupus 1996 Jun
PMID:Antiphospholipid antibodies (aPL) increase the potential monocyte procoagulant activity in patients with systemic lupus erythematosus. 880 91

Fibrinolysis triggered by t-PA bound to fibrin is one of the main antithrombotic mechanisms. Defects in the fibrinolytic system-decreased tissue-type plasminogen activator (t-PA) activity and elevated levels of plasminogen activator inhibitor (PAI-1), in patients with SLE have been associated with an increased tendency to thrombosis. In the present study, 43 patients with SLE fulfilling the ACR criteria for the disease, were studied for the presence of autoantibodies to fibrin-bound t-PA, i.e. the physiological active form of this plasminogen activator. A solution of 200 IU/ml of t-PA was incubated with solid-phase fibrin prepared as previously described (Anal Biochem 1986; 153; 201-210). Sera diluted 1:50 were incubated with fibrin-bound t-PA, the plates were then washed, and bound immunoglobulins were detected using a polyvalent peroxidase-labeled goat anti-human Ig. Plates coated with fibrin alone were used as controls. Sera were considered positive when A490/630 obtained with normal human sera in two independent test was greater than the mean plus 2 SD. Eleven of 43 (26%) SLE sera demonstrated antibody reactivity against fibrin-bound t-PA. Within the anti-t-PA positive group there was a higher proportion of SLE patients with severe Raynaud's phenomenon and thrombotic events when compared to the anti-t-PA negative group: 36% vs 6% and 18% vs 6% respectively. These results suggest that autoantibodies to fibrin-bound t-PA could play a role in the pathogenesis of vascular disease in some SLE patients.
Lupus 1996 Aug
PMID:Antibodies to fibrin-bound tissue-type plasminogen activator in systemic lupus erythematosus are associated with Raynaud's phenomenon and thrombosis. 886 98

Primary hypercoagulable states are hereditary disorders that result in arterial and venous thromboses. The purpose of this report is to present three patients with hypercoagulable states, and offer current guidelines for diagnosis and treatment. Primary hypercoagulable disorders such as antithrombin III, protein C and protein S deficiencies, fibrinolytic disorders such as decreased plasminogen levels and plasminogen activator deficiency, and antiphospholipid syndromes such as anticariolipin antibody and lupus anticoagulants will be reviewed. We will emphasize clinical characteristics that should prompt evaluation for hypercoagulation, appropriate laboratory tests for hypercoagulable disorders, and treatment. Other secondary and recently investigated hypercoagulable disorders, including heparin-associated thrombocytopenia, homocystinemia, lipoprotein (a), plasminogen activator inhibitor, and factor V Leiden, will also be reviewed.
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PMID:The surgical implications of primary hypercoagulable states. 904 71

Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing osteonecrosis (ON). Twenty-six patients with SLE were studied. Fifteen of these had ON and 11 did not. The latter were used as control subjects. Various coagulation analytes including antithrombin III (ATIII) activity, protein C activity, protein S activity, alpha 2-antiplasmin activity, anticardiolipin antibodies (aCL), plasminogen activator inhibitor (PAI-1) activity and tissue type plasminogen activator (tPA) antigen were measured using citrated plasma samples from the patients. A significant proportion (80%) of patients had at least one laboratory abnormality that has been associated with a thrombotic predisposition. ON was significantly associated with elevated levels of PAI-1 activity; it was also associated with elevated PAI-1/tPA ratio. There was no association between ON of SLE and abnormalities of the other measured coagulation analytes. These results suggest that defective fibrinolysis seems to be operative in the pathogenesis of ON associated with SLE. The defect appears to involve an imbalance between tPA and its inhibitor, PAI-1. This imbalance could represent an important risk factor in the pathogenesis of ON.
Lupus 1998
PMID:Association of osteonecrosis in systemic lupus erythematosus with abnormalities of fibrinolysis. 949 48

Antiphospholipid antibodies (aPL) have been found to be associated with arterial and venous thrombosis. Percutaneous transluminal coronary angioplasty (PTCA) is an established therapy for ischaemic heart disease (IHD), which is still affected by restenosis at a rate of 20-30%. This study was aimed at investigating the possible role of aPL in restenosis after PTCA. In sixty consecutive IHD patients, aPL (lupus anticoagulant -LA- and anticardiolipin antibodies -aCL) and markers of haemostatic activation were investigated before PTCA, and patients were followed up for restenosis. No infections, autoimmune disease or treatment by drugs that may alter aPL levels occurred in any of the patients. aPL were found in 15/60 patients: aCL in 7/60, LA in 5/60 and aCL and LA in 3/60. No statistically significant difference was found between aPL negative and aPL positive patients in pre PTCA plasma levels of prothrombin activation fragment (F1+2) 1.4 nmol/l (0.3-5.71) vs 1.4 nmol/l (0.9-4.0), thrombin-antithrombin complex (TAT) 4.0 microg/l (1.1-34.2) vs 5.2 microg/l (2.1-60.0), D-dimer (DD) 25 ng/ml (2-515) vs 44 ng/ml (2-160) or plasminogen activator inhibitor activity (PAI) 4.8 IU/ml (2.5-36.4) vs 4.4 IU/ml (2.5-13.4). Restenosis was observed in 13/60 patients (7/45-15% - aPL negative and 6/15-40% - aPL positive patients) who underwent angiographic tests after PTCA because of recurring angina or positive exercise test. Restenosis occurred after 2.2 months (0.5-3) in aPL positive patients and after 3.5 months (1-12.8) in aPL negative. These results suggest that 1) restenosis with recurrent ischaemia occurs more frequently in aPL positive than in aPL negative patients, 2) in aPL positive patients restenosis occurs earlier, and 3) the presence of aPL is not associated with hypercoagulability.
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PMID:Antiphospholipid antibodies: a new risk factor for restenosis after percutaneous transluminal coronary angioplasty? 960 31


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