Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was performed to investigate the acute effects of physiologically induced hyperinsulinemia on plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (t-PA) and triglycerides (TG). Forty-one male patients with chronic coronary heart disease (CHD) and moderate hypertriglyceridemia were studied for 3 h; 33 of them during an oral glucose tolerance test (OGTT), whereas eight patients served as controls, receiving water only. All subjects in the OGTT group were adequate responders to glucose administration, giving peak values of glucose (median 6.90 mmol l-1) and insulin (median 123 mU l-1) after 1 h. TG were unchanged throughout the test period in both groups. After 1 h PAI-1 activity and antigen decreased significantly more in the OGTT group than in the controls (median values: PAI-1 act 23-12 vs. 12-12 U ml-1; (p < 0.001). PAI-ag 45-35 vs. 18-16 ng ml-1 (p < 0.05)). t-PA increased more in the OGTT group (0.70-1.20 vs. 0.50-0.63 IU ml-1 (p = 0.08)). These differences tailored off after 3 h. We conclude that acute hyperinsulinemia, when generated during an OGTT, stimulates fibrinolysis with a consequent decrease in PAI-1 activity, but give no change in TG. The postulated regulating role of insulin for the steady state levels of PAI-1 could probably not be elucidated in the present dynamic model.
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PMID:Insulin and PAI-1 levels during oral glucose tolerance test in patients with coronary heart disease. 803 49

A plasminogen activator (PA) system is involved in ovulation, implantation, tumor invasion and metastasis. In order to clarify the regulation of this PA system in endometrial cells, we examined which agent affecting cellular function altered tissue-type plasminogen activator (t-PA) secretion by endometrial carcinoma cell line (KLE cells) in vitro. Triiodothyronine, retinoic acid, insulin, 8-bromo-cAMP, PDGF, IGF-I, basic FGF or TNF-alpha did not alter t-PA secretion while the activator of protein kinase C, phorbol myristate acetate (PMA) stimulated t-PA secretion in a dose-dependent fashion (10(-10)-10(-8) M). The time required to give a statistically significant increase in t-PA over control was 3 hours, and the maximal increase was seen after 24 hours of exposure. Another active phorbol ester, PDD also stimulated t-PA secretion while inactive forms of phorbol ester, 4 alpha-PDD and phorbol did not alter it. Cholera toxin or 8-bromo-cAMP did not affect t-PA secretion, but enhanced PMA-stimulated t-PA secretion. Cycloheximide and actinomycin D completely abolished PMA-stimulated t-PA secretion. These results suggest that (1) t-PA secretion in the endometrial carcinoma cell is modulated by a protein kinase C system, (2) This effect is through new RNA production and protein synthesis. (3) There is a complicated relationship between protein the kinase C and protein kinase A system as to the regulation of t-PA secretion. This would be a suitable model to clarify the PA system in endometrial cells.
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PMID:[Effect of phorbol ester on tissue-type plasminogen activator (t-PA) secretion in endometrial carcinoma cell line in vitro]. 812 84

The relation of habitual diet and cardiorespiratory fitness to plasma fibrinogen concentration, Factor VII activity (F VIIc), Factor X activity (F X), tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1) concentrations, anti-thrombin III (AT III) and apolipoprotein(a) (Apo[a]) was analyzed in 111 normolipidemic men aged 51-53 years. Diet was evaluated by seven day food records. Maximal oxygen consumption and aerobic threshold were determined in maximal bicycle ergospirometry test based on breath-by-breath analysis of expired respiratory gas. Plasma fibrinogen was measured by thrombin method, F VIIc by one-stage coagulation method, AT III and F X colorimetrically, t-PA and PAI-1 antigens by ELISA and Apo(a) concentration radioimmunologically. Carbohydrate intake was negatively (r = -0.31, p < 0.001; r = -0.24, p < 0.01; r = -0.36, p < 0.001) and fat intake positively (r = 0.24, p < 0.01; r = 0.29, p < 0.001; r = 0.32, p < 0.001) related to F X, PAI-1, and t-PA, respectively. Aerobic threshold correlated negatively with fibrinogen (r = -0.33, p < 0.001) and F X (r = -0.30, p < 0.001). Fasting insulin was the strongest determinant for PAI-1 (r = 0.55, p < 0.001) and a significant positive correlate to F VIIc (r = 0.30, p < 0.001), F X (r = 0.28, p < 0.01) and t-PA (r = 0.47, p < 0.001). These data emphasize the importance that carbohydrate rich diet and cardiorespiratory fitness may have against thrombogenesis.
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PMID:Relation of habitual diet and cardiorespiratory fitness to blood coagulation and fibrinolytic factors. 819 95

Microalbuminuria is an important risk factor for cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM) patients although the pathogenic mechanism between microalbuminuria and cardiovascular disease has not yet been established. Microalbuminuria in insulin-dependent diabetes mellitus (IDDM) patients has been related to abnormalities in haemostasis, poor glycaemic control, disadvantageous alterations in the lipid spectrum and elevated concentrations of lipoprotein(a), another independent risk factor for cardiovascular disease. In this study the interrelations between microalbuminuria and metabolic control, lipoprotein(a), other blood lipids and several haemostasis parameters were studied in 96 NIDDM patients (50 women, 46 men). Forty-three patients showed microalbuminuria. No significant differences were found in blood lipids (Lp(a), serum cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides), glycaemic control (HbA1c) and several haemostasis parameters (factor VII, VIII, fibrin monomer, thrombin-antithrombin III, D-dimer, tissue plasminogen activator antigen and plasminogen activator inhibitor-1) between the micro- and normoalbuminuric subgroups. In the microalbuminuric subgroup increased concentrations for plasminogen and alpha 2-antiplasmin were measured. In general, the presence of microalbuminuria was not associated with significant alterations in glycaemic control, blood lipids or haemostasis parameters in this group of 96 NIDDM patients. Further investigation is required to explain the excess cardiovascular mortality in patients with an elevated urinary albumin excretion rate.
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PMID:The effect of microalbuminuria on glycaemic control, serum lipids and haemostasis parameters in non-insulin-dependent diabetes mellitus. 825 Apr 95

Accelerated atherosclerosis is the leading cause of death in patients with non-insulin-dependent diabetes mellitus (NIDDM). Impaired endogenous fibrinolytic activity may accelerate atherosclerosis by exposing vascular luminal wall surfaces to persistent and recurrent thrombi and clot-associated mitogens. This study was conducted to further characterize endogenous fibrinolysis in lean and obese nondiabetic subjects and in NIDDM patients and to identify mechanisms responsible for the alterations identified. Obese and diabetic subjects had threefold elevations of plasma concentrations of plasminogen activator inhibitor type 1 (PAI-1) compared with values in lean control subjects. Despite the lack of significant differences in plasma concentrations of tissue-type plasminogen activator in the obese and diabetic subjects, both basal and stimulated endogenous fibrinolytic activities were decreased. The decreases were associated with increased activity of PAI-1 in plasma, in turn correlated with increased concentrations of immunoreactive insulin and C-peptide. These results are consistent with our previous observations demonstrating direct stimulatory effects of insulin and its precursors on cellular expression of PAI-1 in vitro and observations by others demonstrating decreased basal fibrinolytic activity in NIDDM patients. Impaired endogenous fibrinolytic activity could lead to prolonged or recurrent exposure of luminal surfaces of vessel walls to microthrombi and clot-associated mitogens that may accelerate atherosclerosis in hyperinsulinemic subjects.
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PMID:Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients. 826 7

Microalbuminuria is associated with an increased risk of cardiovascular disease (CVD) in insulin-dependent diabetes mellitus (IDDM) patients, but the pathophysiological basis of this association is not clear. To see whether or not hemostatic dysfunctions might contribute to explain this association, we measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), factor VII activity, plasma fibrinogen, and plasma endothelin-1 (ET-1) in 13 microalbuminuric (albumin excretion rate [AER], 20-200 micrograms/min) and in 13 comparable normoalbuminuric (< 20 micrograms/min) IDDM patients. t-PA and ET-1 were similar in the two groups, whereas PAI-1 activity (5.65 +/- 1.92 vs. 0.85 +/- 0.58 IU/ml, P < 0.05), factor VII (87.85 +/- 4.94 vs. 76.54 +/- 2.31%, P < 0.05), and plasma fibrinogen (3.38 +/- 0.21 vs. 2.65 +/- 0.13 g/l, P < 0.05) were significantly higher in microalbuminuric than in normoalbuminuric patients. Plasma fibrinogen was related to AER (r2 = 0.23, P < 0.05), whereas triglycerides and factor VII were related to PAI-1 (r2 = 0.39, P < 0.001 and r2 = 0.10, P < 0.05). These results suggest that microalbuminuria is associated with a hypercoagulative and hypofibrinolytic state. Hemostatic dysfunctions might be a pathogenetic link between microalbuminuria and CVD.
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PMID:PAI-1 and factor VII activity are higher in IDDM patients with microalbuminuria. 831 15

1. The effects of venous occlusion on the coagulation and fibrinolytic systems were investigated in six patients with type 1 (insulin-dependent) diabetes and 11 age- and sex-matched non-diabetic control subjects. The coagulation parameters (fibrinogen, prothrombin time, partial thromboplastin time with kaolin, von Willebrand factor antigen) did not differ between patients and control subjects either before or after 20 min of venous occlusion. No rise was observed in von Willebrand factor antigen after venous occlusion in either group. 2. In the diabetic patients, chronic activation of the fibrinolytic system was found at baseline, which was indicated by a shortened euglobulin lysis time (P < 0.01), increased tissue plasminogen activator activity (P < 0.05) and decreased plasminogen activator inhibitor type 1 antigen level (P < 0.05), when compared with control subjects. In both groups venous occlusion resulted in significant increments in all measurements, except plasminogen activator inhibitor type 1 antigen level. The post-occlusion values did not differ between the two groups, except the plasminogen activator inhibitor type 1 antigen level, which remained significantly lower in the diabetic patients. The mean increments in each parameter did not differ between the two groups. 3. Coagulation and fibrinolysis were assessed in response to acute insulin-induced hypoglycaemia. Von Willebrand factor antigen levels increased significantly in both groups, with no difference in maximal increments. Significant activation of the fibrinolytic system occurred in response to hypoglycaemia, demonstrated by shortened euglobulin lysis time and increased fibrin plate lysis, tissue plasminogen activator antigen level and tissue plasminogen activator activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coagulation and fibrinolytic systems in type I diabetes: effects of venous occlusion and insulin-induced hypoglycaemia. 838 39

Eleven healthy subjects volunteered to participate in a fiber supplement study and were instructed to consume oat husk tablets in addition to their regular diets. During a 2-week experimental period the subjects consumed 10 g oat husk per day. Blood samples were collected before breakfast between 8:00 and 9:00. As compared to baseline, 10 g oat husk supplementation per day resulted in a reduction of plasma plasminogen activator inhibitor type 1 (PAI-1) activity (p < 0.05). Except for an increase in glucose, no other statistically significant deviation from baseline was observed in measured blood parameters; tissue plasminogen activator activity, prourinary plasminogen activator, coagulation factor VII, total cholesterol, HDL cholesterol, LDL cholesterol, lipoprotein (a), triglycerides and insulin. A 6-week washout period returned the PAI-1 activity level to baseline.
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PMID:Oat husk fiber decreases plasminogen activator inhibitor type 1 activity. 838 89

Elevated plasma levels of fibrinogen, factor VII coagulant activity (F VIIc), and plasminogen activator inhibitor (PAI-1) have been reported to be strictly associated with thrombotic events and are considered to be important risk markers of atherothrombotic cardiovascular disease. Therefore, we evaluated in 15 patients on continuous ambulatory peritoneal dialysis (CAPD) the plasma levels of these coagulation factors, basal insulin values, and the lipid pattern in comparison with 33 hemodialysis (HD) patients and 59 healthy subjects. In CAPD the total cholesterol and triglyceride results were significantly increased, but no difference was found in HDL cholesterol. Fibrinogen and F VIIc results were significantly higher in CAPD and HD than in the control group, probably due to an increased hepatic synthesis as a nonspecific response to the peritoneal protein loss. Elevated F VIIc activity may be caused by the presence of large negatively charged lipoproteins, in vivo thrombin formation, or reduced hepatic clearance. Both PAI 1 and t-PA results were higher in CAPD, probably due to an increased synthesis by endothelial cells activated by glucose peritoneal absorption and hypertonic dialysis solutions. The contemporary elevation of fibrinogen, F VIIc, PAI-1, and t-PA suggests that CAPD patients present a hypercoagulability and hypofibrinolysis condition, which may promote the development of atherothrombotic events.
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PMID:Risk factors of ischemic cardiac disease in patients on continuous ambulatory peritoneal dialysis. 839 23

Patients with hyperinsulinemia, defined by increased concentrations of IRI in plasma, experience increased cardiovascular mortality. In type II diabetic patients, the increase in IRI may reflect, in part, not only insulin but also proinsulinemia as a result of impaired conversion of proinsulin to insulin by pancreatic beta-cells. High IRI is accompanied by attenuation of endogenous fibrinolytic activity and increased plasma PAI-1, the primary physiological inhibitor of t-PA. Concordant increases of plasma PAI-1 and plasma IRI appear to reflect direct effects of insulin and proinsulin on the synthesis and secretion of PAI-1 by endothelial and liver cells as judged from results of studies in vitro. Because attenuated fibrinolysis may predispose to thrombosis, the increased exposure of luminal surfaces of vessels to atherogenic, clot-associated mitogens and chemoattractants may activate macrophages and potentiate proliferation of vascular smooth muscle cells. Accordingly, increased concentrations of plasma IRI may contribute to macrovascular disease in diabetic patients by impairing endogenous fibrinolysis.
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PMID:Attenuated fibrinolysis and accelerated atherogenesis in type II diabetic patients. 842 Aug 6


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