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)

We investigated the effect of plasma and serum from 10 subjects with the lupus anticoagulant and thrombosis and 9 normal subjects on the secretion of tissue-type plasminogen activator (t-PA) and its rapid inhibitor (type 1 plasminogen activator inhibitor, or PAI-1) by cultured human endothelial cells. Confluent monolayers of human umbilical vein endothelial cells were incubated for 48 hours with plasma or serum diluted ten-fold in serum-free endothelial cell growth medium, and the secretion of t-PA and PAI-1 measured by enzyme-linked immunosorbent assay. No consistent differences in mean t-PA and PAI-1 release were found between cells exposed to normal plasma or serum and plasma or serum from subjects with the lupus anticoagulant and thrombosis. No plasma or serum sample produced consistent inhibition of t-PA release or stimulation of PAI-1 release (defined as t-PA levels less than the mean minus two standard deviations for normal subjects, and PAI-1 levels greater than the mean plus two standard deviations for normal subjects, respectively). These findings do not support a role for altered endothelial fibrinolytic activity in the pathogenesis of thrombosis in subjects with the lupus anticoagulant, and are consistent with previous observations that these subjects have normal fibrinolytic activity in vivo.
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PMID:Effect of the lupus anticoagulant on endothelial fibrinolytic activity in vitro. 250 1

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

This review has stressed the common hereditary and acquired blood protein defects associated with thrombosis. The most common of the hereditary defects appear to be antithrombin, protein C, and protein S deficiency, and the most common acquired defects are anticardiolipin antibodies and the lupus anticoagulant. Therefore, these are the defects which should first be searched for in an individual with unexplained thrombosis. If these more common defects are not found, the rarer defects, including HC-II, plasminogen, or TPA deficiency, dysfibrinogenemia, elevated PAI-1, or heterozygous homocystinemia should be looked for. The incidence of activated protein C co-factor deficiency (APC resistance) is not yet clear but may also represent a common defect. PAI-1 defects may, with time, be shown to be common. Finding these defects has important implications for therapy for the individual patient and for the institution of family studies to identify, inform, and possibly treat others at risk. It is expected that as knowledge of hemostasis expands, more hereditary and acquired defects, such as elevated lipoprotein(a) or defects of extrinsic (tissue factor) pathway inhibitor (EPI, TFPI), may be associated with enhanced risks for thrombosis.
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PMID:Blood protein defects associated with thrombosis. Laboratory assessment. 778 Dec 75

Activated protein C (APC)-protein C inhibitor (PCI) complex and APC-alpha 1antitrypsin (alpha 1AT) complex levels were measured in 29 patients positive for lupus anticoagulant (LA). LA was considered positive if two of the following three criteria were fulfilled: (1) prolongation of the activated partial thromboplastin time, (2) prolongation of the kaolin clotting time (KCT) and KCT mixing test, and (3) prolongation of the dilute Russell's viper venom time (DRVVT) and DRVVT/DRVVT with high lipid concentration. Plasma thrombin-antithrombin III (AT-III) complex and plasmin-alpha 2-antiplasmin inhibitor complex levels in patients positive for LA were increased slightly, but not significantly, and FDP-D-dimer and t-PA levels were not markedly increased. Plasma PAI-1 level in the LA-positive patients was significantly increased compared with normal volunteers. AT-III activity, protein C antigen, PCI antigen, and protein S antigen levels in the LA-positive patients were virtually normal, while protein C activity was slightly, but not significantly, decreased. APC-PCI complex level was increased in all LA-positive patients, and was not detectable in patients with systemic lupus erythematosus and normal volunteers. APC-alpha 1AT complex was increased slightly, in only two LA-positive patients; it was not detectable in the other patients or in the normal volunteers. These findings suggest that patients positive for LA are in a hypercoagulable state and that protein C activity in such patients is decreased, due to the activation of this protein.
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PMID:Increased activated protein C-protein C inhibitor complex level in patients positive for lupus anticoagulant. 805 49

This review has stressed the common hereditary and acquired blood protein defects associated with thrombosis. The most common of the hereditary defects appear to be antithrombin, protein C, and protein S deficiency and the most common acquired defects are anticardiolipin antibodies and the lupus anticoagulant. Therefore these are the defects that should first be looked for in an individual with unexplained thrombosis. If these more common defects are not found, then the rarer defects, including heparin cofactor II, plasminogen or tissue plasminogen activator deficiency, dysfibrinogenemia, or elevated PAI-1 should next be sought. The importance of finding these defects has significant implications for therapy of the individual patient and for institution of family studies to identify, inform, and possibly treat others at risk. It is expected that as knowledge of hemostasis expands, more hereditary and acquired defects, such as elevated lipoprotein(a) or defects of extrinsic (tissue factor) pathway inhibitor may be associated with enhanced risks of thrombosis.
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PMID:Syndromes of hypercoagulability and thrombosis: a review. 805 29

In western countries, acute myocardial infarction is the commonest cause of morbidity and mortality [19]. An occlusive coronary thrombus on an ulcerated atherosclerotic plaque in the coronary arteries is the etiological event in more than 90% of patients with Q-wave myocardial infarction [38]. The underlying abnormality in non-Q-wave myocardial infarction is often a ruptured atherosclerotic plaque, which acts as a nidus for the deposition and activation of platelets. In this case, thrombosis occurs, but may not be totally occlusive, or an early spontaneous recanalization may occur. On the other hand, some clinical trials showed that a prolonged treatment with antiplatelet drugs significantly reduces the recurrence of coronary ischemia. Thus, atherosclerosis is a necessary condition for myocardial infarction, but it is not sufficient in that it usually needs the occurrence of thrombosis. However, only 25-30% of these thrombotic events are prevented by the administration of antiplatelets drugs. In recent years, epidemiological studies identified some hemostatic parameters whose abnormalities may help predict the risk of ischemic events: fibrinogen [14], plasminogen activator inhibitor-1 (PAI-1) [3], lipoprotein(a) [46], anticardiolipin antibodies (ACA) and lupus anticoagulant (LA) [10], leukocyte count [34], blood viscosity [34]. Some of these, such as fibronogen and PAI-1 are acute-phase proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma predictors of ischemic complications of atherosclerosis: open issues. 806 Dec 44

This article has stressed the common hereditary and acquired blood protein defects associated with thrombosis. The commonest hereditary defects appear to be antithrombin, protein C, and protein S deficiency, and the commonest acquired defects are anticardiolipin antibodies and the lupus anticoagulant. Therefore these are the defects that should first be looked for in an individual with unexplained thrombosis. If these commoner defects are not found, the rarer defects, including HC-II, plasminogen or t-PA deficiency, dysfibrinogenemia, or elevated PAI-1, should next be sought. The incidence of activated protein C cofactor deficiency is not yet clear but may also represent a common defect. Likewise, PAI-1 defects may, with time, be shown to be quite common. The importance of finding these defects has significant implications for therapy of the individual patient and for institution of family studies to identify, inform, and possibly treat others at risk. It is expected that as knowledge of hemostasis expands, more hereditary and acquired defects, such as elevated lipoprotein (a) or defects of extrinsic (tissue factor) pathway inhibitor may be associated with enhanced risks of thrombosis.
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PMID:Hypercoagulability and thrombosis. 817 Feb 63

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

We identified a group of 24 young (less than 50 years of age) women with isolated, premature atherosclerotic aortoiliac occlusive disease and attempted to identify distinguishing hemostatic characteristics. Most of these patients (62%) presented with acute thromboembolic events (blue toe syndrome, n = 6; macroemboli, n = 6; or aortoiliac thrombosis, n = 3). Aortoiliac reconstruction (aortoiliac endarterectomy, n = 10, aortobifurcation bypass grafts, n = 6; and percutaneous angioplasty, n = 4) was complicated by early thrombosis in 6 of 20 cases (30%), (1 of 10 endarterectomies, 4 of 6 bypass grafts, and 1 of 4 angioplasties). Fresh thrombus overlying an atherosclerotic plaque was a common finding at surgery. This observation and the relatively high incidence of thromboembolic events led us to hypothesize that a characteristic hemostatic profile might underlie the remarkably similar clinical presentations of these women. Levels of antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant), plasminogen activator inhibitor-1, fibrinogen, antithrombin III, protein C, protein S, plasminogen, prothrombin fragment F1 + 2, and D-dimer were determined for these young women and for 21 age-matched white female control subjects without vascular disease and nine white male patients with aortoiliac occlusive disease (mean 61 years, range 43 to 74 years). The incidence of anticardiolipin antibodies was 42% (8 of 19) in the female patients, which was significantly elevated (p = 0.028). The female (62.5%) and male (100%) patients had significantly elevated D-dimer levels (p < 0.001). Deficiencies of antithrombin III, protein C, and protein S were rare. A unique pattern of premature aortoiliac atherosclerosis exists in some young women. Intra-arterial thromboembolic events are common at presentation and complicate surgical management. The role of antiphospholipid antibodies remains uncertain.
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PMID:Young women with advanced aortoiliac occlusive disease: new insights. 898 71

Quantitative reverse transcription polymerase chain reaction and in situ hybridization were employed to investigate the expression of tissue-type and urokinase-type plasminogen activators (t-PA and u-PA, respectively), of their specific inhibitor (PAI-1), and of the procoagulant molecule tissue factor (TF) in tissues from mice that develop autoimmune disease (MRL lpr/lpr). A dramatic increase in PAI-1 activity in plasma and in PAI-1 mRNA in the kidneys was observed in these mice, and this increase appeared to correlate with the progression of lupus nephritis. The increase in PAI-1 mRNA was relatively specific for the kidney as little or no change was observed in most other tissues. One exception was the brain where PAI-1 mRNA was also significantly higher in the diseased mice. In addition to these changes in PAI-1, decreases in u-PA mRNA and increases in TF mRNA were demonstrated in kidneys from the lupus-prone mice. These changes also correlated with the development of lupus nephritis and with spontaneous glomerular and peritubular fibrin deposition in the nephritic kidney. In this regard, the MRL lpr/lpr mice were found to be considerably more sensitive to endotoxin than the normal controls, developing fibrin deposits in the kidneys and other tissues at 10- to 20-fold lower concentrations of this toxic agent. The increase in PAI-1 and TF mRNAs and the decrease in u-PA mRNA in the kidneys of MRL lpr/lpr mice suggests that changes in the expression of these genes may promote the formation of microthrombi and thus contribute to the progression of lupus nephritis in this model.
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PMID:The kidneys of mice with autoimmune disease acquire a hypofibrinolytic/procoagulant state that correlates with the development of glomerulonephritis and tissue microthrombosis. 928 21


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