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

Fibrinolytic activities on cases with chronic renal failure, 13 cases at pre and post introduction of hemodialysis and 40 cases at pre and post hemodialysis of maintenance hemodialysis with 38 normal controls were investigated. The plasminogen activator of untreated chronic renal failure was lower than controls, yet increased with the introduction of hemodialysis. On the other hand the antiplasmin was lowered with the introduction. In cases with maintenance hemodialysis, the plasminogen activator was lower than controls, but was elevated with hemodialysis. The level of antiactivator was higher in uremia of either pre or post hemodialysis than controls. The levels of alpha 2-macroglobulin and alpha 1-antitrypsin were reduced at prehemodialysis state comparing to controls, and yet, increased with hemodialysis, respectively. The low molecular weight antiplasmin and antiactivator, molecular weight below 30,000 were separated with Sephadex G-50 gel filtration of plasma. The low molecular weight fibrinolysis inhibitors of plasma with untreated uremia were elevated comparing to controls, but decreased with the hemodialysis. The removable fibrinolytic inhibitors were indicated, however, the ratio of the low molecular weight fibrinolytic inhibitors to the total fibrinolytic inhibitors were little.
 ...
PMID:Studies of fibrinolytic activity of uremic and longterm hemodialytic patients with special reference to fibrinolytic inhibitor. 12 65

Accelerated atherosclerosis is a serious complication of chronic renal failure (CRF) treated by peritoneal dialysis. In order to study the pathological mechanisms underlying its development we are using an animal model, namely the C57BL/6J mouse, which develops foam cell-type atherosclerotic lesions after surgical induction of CRF. During atherogenesis, monocyte/macrophages move from the circulation to the blood vessel wall, migrate through the endothelium, imbibe lipid and transform into foam cells. Migration through the endothelium involves proteolysis by plasminogen activator (PA) and uptake of lipids involves hydrolysis of lipoproteins by lipoprotein lipase (LPL). Both of these enzymes are secreted by macrophages. In this paper we report the results of studies on the effect of uremia on the secretion of PA and LPL by macrophages from C57BL/6J mice. The secretion of PA and LPL by macrophages from uremic mice (as defined by BUN levels) was higher than that by cells from control animals. Furthermore, whereas macrophage secretion of PA and LPL was significantly less in normal mice fed a high fat diet than in mice fed rodent chow, it was increased above control levels in uremic animals fed the atherogenic diet. We conclude that increased secretion of PA and LPL by macrophages may contribute to atherogenesis in uremic C57BL/6J mice.
 ...
PMID:Macrophage secretory activity and atherosclerosis during chronic renal failure. 198 12

A simple method for the quantitative assay of vascular plasminogen activator is described. From 24 chronic renal failure patients who were undergoing surgery for A/V fistular or shunt construction, small pieces of artery (mean 7.8 mg, range 3.0-18.5 mg) and vein (mean 4.5 mg, range 3.0-8.8 mg) were used. The fibrinolytic activity was assayed on a well-controlled fibrin plate by only distilled water immersion and incubation at 37 degrees C. Basal fibrinolytic activity was correlated with venous fibrinolytic activity (r = 0.773, p less than 0.0001) and with arterial fibrinolytic activity (r = 0.55, 0.005 less than p less than 0.01). The increment of fibrinolytic activity by venous occlusion was correlated to venous fibrinolytic activity (r = 0.849, p less than 0.0001) but not to arterial fibrinolytic activity (r = 0.34, 0.1 less than p less than 0.25).
 ...
PMID:A simple quantitative assay of vascular plasminogen activator--not only stimulated fibrinolytic activity but also basal fibrinolytic activity are correlated with venous fibrinolytic activity. 209 97

This study was designed to evaluate platelet activation, enhancement of coagulation and fibrinolysis in patients with chronic renal failure on long-term haemodialysis. Beta thromboglobulin (BTG), platelet factor 4 (PF4), fibrinopeptide A, tissue plasminogen activator (t-PA) activity and antigen, tissue plasminogen activator inhibitor (PAI), fibrin, and fibrinogen degradation products were studied during dialysis. The influence of two types of membrane on these parameters was also evaluated. The patients comprised 24 individuals on long-term haemodialysis on either cuprophan membrane (CUP) (12 patients) or polyacrylonitrile membrane (AN 69) (12 patients). Blood samples were collected before, at 15 min, and at the end of dialysis. The results demonstrated that platelet activation was permanent and increased during haemodialysis. However, no difference could be demonstrated between patients treated on CUP and patients treated on AN 69. Coagulation was also enhanced permanently but did not show modification during haemodialysis. Fibrinolysis was activated at the end of haemodialysis in half the patients, but again no difference could be demonstrated between patients treated on AN 69 and CUP membranes. It was concluded that the process of haemodialysis itself enhanced platelet activation, coagulation, and fibrinolysis but that both membranes were of equal effect.
 ...
PMID:Activation of platelets, coagulation and fibrinolysis in patients on long-term haemodialysis: influence of cuprophan and polyacrylonitrile membranes. 214 56

We have studied vessel wall function in two groups of patients with chronic renal failure - 1) conservative treatment only and 2) maintenance hemodialysis. Three proteins synthesized by vascular endothelium-plasminogen activator (PA), factor VIII related antigen (VIII:RAg) and antithrombin III (ATIII) - were assayed before and after a fifteen minute period of venous occlusion. The release of PA was significantly reduced in patients on maintenance hemodialysis as compared to both undialyzed uremics and controls. Lesser amounts of VIII:RAg were also released by hemodialysis patients than by undialyzed uremics. These defects, which are suggestive of vessel wall dysfunction on maintenance hemodialysis, may contribute to the high incidence of arteriopathy and thrombotic disease observed in this group of patients.
 ...
PMID:Impaired vessel wall response to venous occlusion in patients with chronic renal failure on maintenance hemodialysis. 644 60

The overall fibrinolytic activity is depressed in patients with chronic renal failure where a prothrombotic state is described, thereby enhancing the risk of vascular occlusive events. The mechanism responsible for fibrinolysis derangement has not yet been elucidated. To evaluate the effect of the uremic environment on the fibrinolytic activity of endothelial cells, we studied plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) production by human umbilical vein endothelial cells (HUVEC) in culture, exposed either to uremic or normal sera, before and after cytokine stimulation. Twenty uremics were studied: 11 were on conservative dietary treatment and nine were on maintenance hemodialysis. Eight healthy subjects served as controls. Before cytokine stimulation, no difference in the HUVEC supernatant concentration of t-PA and PAI-1 was found among the groups studied. After stimulation with interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, the HUVEC supernatant levels of PAI-1 in the uremics were higher than in the controls, whereas the supernatant levels of t-PA did not differ. Our data provide evidence that uremic serum, in concert with IL-1 or TNF-alpha, can enhance PAI-1 secretion by endothelial cells, thereby depressing the fibrinolytic system. This impaired endothelial fibrinolytic response to hypercoagulation could favor vascular events, which are the major cause of morbidity and mortality in patients with chronic uremia.
 ...
PMID:Uremic medium increases cytokine-induced PAI-1 secretion by cultured endothelial cells. 980 72

Plasma Lp (a) concentration and activation of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1(PAI-1) were determined in 50 patients with chronic renal failure (CRF) and in 50 healthy subjects. The results demonstrated that plasma concentration of Lp(a) was significantly higher and plasma t-PA activation was significantly lower in CRF patients than in healthy subjects. With multivariate analyses, plasma Lp(a) concentration was positively correlated with the total amount of 24 h uric protein, plasma BUN and uric protein concentration. Moreover, a negative significant correlation between plasma Lp(a) levels and t-PA activation was observed. Plasma Lp(a) levels did not show a correlation to PAI-1 activation. It is indicated that renal function may contribute to moderate plasma Lp(a) concentration and elevated Lp(a) levels may be related with fibrinolytic impairment.
 ...
PMID:[Plasma Lp (a) levels and correlation of Lp (a) with fibrinolysis activation in chronic renal failure]. 1208 Jun 50

The best known function of the fibrinolytic system is its ability to dissolve blood clots. The key enzyme of fibrinolysis, plasmin, is formed by conversion from plasminogen through the action of activators, the most important of which is tissue type plasminogen activator (tPA). Low levels of tPA or excessive levels of plasminogen activator inhibitor-I (PAI-I) cause hypofibrinolysis, causally related to the development of atherosclerosis and associated thrombotic complications, as well as with the development of venous and arterial thrombosis. A chronic decrease in renal function leads to hypofibrinolysis due primarily to low levels of tPA. Hypofibrinolysis is present both in patients treated by long-term hemodialysis and by peritoneal dialysis. The hemodialysis procedure acutely raises the plasma levels of tPA, primarily as a result of the bioincompatibility of materials in the extracorporeal circuit. In peritoneal dialysis, dialysis solution dwell time is associated with an increase in PAI-I levels in the abdominal cavity. Fibrinolysis defects occur also in renal transplant recipients. In transplant patients, the main abnormality is also hypofibrinolysis which, however, unlike the situation with the other methods of renal replacement therapy, is secondary to a rise in PAI-I. A role in the increase of the plasma levels of PAI-I in transplant patients is played by steroid- and cyclosporine-based immunosuppression, most likely by metabolic disorders such as insulin resistance or dyslipoproteinemia, and by genetic factors. Animal experiments with chronic rejection have shown abnormalities in local fibrinolysis in the graft, particularly increased PAI-I expression. Fibrinolysis defects may contribute to an early and frequent development of atherosclerosis in patients with chronic renal failure, to chronic dysfunction of the renal transplant, or to peritoneal fibrosis and peritoneal catheter obstruction in patients on peritoneal dialysis. The exact role of hypofibrinolysis in the development of these complications, and the potential for modulating it, warrant further research.
 ...
PMID:Fibrinolysis in chronic renal failure, dialysis and renal transplantation. 1222 2