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

Lupus anticoagulants (LA) are IgG or IgM antibodies against phospholipids which in vivo represent an important thrombophilic factor despite their in vitro anticoagulant activity. We investigated the fibrinolytic system of 20 patients with connective tissue disease and positive LA, compared to a control group of 24 age- and disease-matched patients without LA. There was no statistically significant difference of alpha 2-antiplasmin, plasminogen, fibrinogen, t-PA activity, D-dimers and heparin cofactor II, between the two groups. Although t-PA was uniformly low in both groups, plasminogen activator inhibitor activity (PAI) was significantly higher in LA cases (p less than 0.001). Increased PAI levels represent an inhibitory factor of the fibrinolytic defense mechanism, which together with other functional deviations may contribute to the thrombophilic tendency of LA patients.
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PMID:Impaired fibrinolysis as an essential contribution to thrombosis in patients with lupus anticoagulant. 250 94

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

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

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

Antibodies to prothrombin have been associated with venous and arterial thrombosis, and they cross-react with a structurally closely related protein plasminogen. We immunised 16 mice with human prothrombin and 15 mice with human plasminogen. Mice immunised with prothrombin developed cross-reactive antibodies to plasminogen (12/16), beta2-glycoprotein I (4/16), tissue-type plasminogen activator (6/16) and cardiolipin (11/16). Mice immunised with plasminogen developed cross-reactive antibodies to prothrombin (8/15), tissue-type plasminogen activator (2/12) and cardiolipin (5/12). Functional effects of antibodies were examined. Immunisation with prothrombin induced lupus anticoagulant activity in 9/14 mice. In mice immunised with plasminogen, radial fibrinolysis was inhibited in 8/10 and plasminogen activation in the chromogenic assay was inhibited in 9/11. No cross-functionality was observed. In conclusion, antibodies to prothrombin and plasminogen cross-react in vivo. Antibodies to prothrombin and plasminogen have different functional profiles, immunisation with prothrombin leads to prolonged blood clotting time, and immunisation with plasminogen induces antibodies interfering with fibrinolysis.
Lupus 2001
PMID:Immunologic and hematologic properties of antibodies to prothrombin and plasminogen in a mouse model. 1123 22

Antiphospholipid antibodies (aPL), the majority of which are directed against beta(2)-glycoprotein I (beta(2)GPI), are associated with an increased incidence of venous and arterial thrombosis. The pathogenesis of antiphospholipid/anti-beta(2)GPI-associated thrombosis has not been defined, and is likely multifactorial. However, accumulating evidence suggests an important role for endothelial cell activation with the acquisition of a procoagulant phenotype by the activated endothelial cell. Previous work demonstrated that endothelial activation by antiphospholipid/anti-beta(2)GPI antibodies is beta(2)GPI-dependent. We extended these observations by defining annexin A2 as an endothelial beta(2)GPI binding site. We also observed that annexin A2 plays a critical role in endothelial cell activation induced by anti-beta(2)GPI antibodies, and others have described direct endothelial activation by anti-annexin A2 antibodies in patients with aPL . Similar findings have been reported using human monocytes, which also express annexin A2. Because annexin A2 is not a transmembrane protein, how binding of beta(2)GPI/anti-beta(2)GPI antibodies, or anti-annexin A2 antibodies, to endothelial annexin A2 causes cellular activation is unknown. Recent studies, however, suggest an important role for the Toll-like receptor family, particularly TLR4. In this article, we review the role of these interactions in the activation of endothelial cells by aPL . The influence of these antibodies on the ability of annexin A2 to enhance t-PA-mediated plasminogen activation is also discussed.
Lupus 2008 Oct
PMID:Annexin A2: biology and relevance to the antiphospholipid syndrome. 1882 60