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)

Based on previous cross-sectional findings, we hypothesized that weight loss could improve several hemostatic factors associated with cardiovascular disease. In a randomized controlled trial, moderately overweight men and women were assigned to one of four weight loss treatment groups or to a control group. Measurements of plasminogen activator inhibitor-1 (PAI-1) antigen, tissue-type plasminogen activator (t-PA) antigen, D-dimer antigen, factor VII activity, fibrinogen, and protein C antigens were made at baseline and after 6 months in 90 men and 88 women. Net treatment weight loss was 9.4 kg in men and 7.4 kg in women. There was no net change (p > 0.05) in D-dimer, fibrinogen, or protein C with weight loss. Significant (p < 0.05) decreases were observed in the combined treatment groups compared with the control group for mean PAI-1 (31% decline), t-PA antigen (24% decline), and factor VII (11% decline). Decreases in these hemostatic variables were correlated with the amount of weight lost and the degree that plasma triglycerides declined; these correlations were stronger in men than women. These findings suggest that weight loss can improve abnormalities in hemostatic factors associated with obesity.
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PMID:Impact of weight loss on plasminogen activator inhibitor (PAI-1), factor VII, and other hemostatic factors in moderately overweight adults. 842 53

The increase in cardiovascular risk associated with having non-insulin-dependent diabetes mellitus (NIDDM) is far greater in women than men. Conventional risk factors do not account for this excess, and attention has focused on the possible contribution of abnormalities of fibrinolysis and coagulation in NIDDM. In the general population a number of hemostatic factors have been shown to predict the occurrence or progression of coronary artery disease. To investigate sex differences in coagulation and fibrinolysis in NIDDM, we measured levels of fibrinogen, factor VII:C, von Willebrand factor, plasminogen activator inhibitor-1, and tissue plasminogen activator in 213 NIDDM subjects (124 men and 89 women) who were not receiving insulin therapy. The women had higher levels of factor VII:C (144% versus 120.5% in men, P < .0005) and plasminogen activator inhibitor-1 activity (25.6 versus 17.0 U/mL), and these differences remained significant when account was taken of the higher body mass index (29.6 versus 28.0 kg/m2, P = .02), glycosylated hemoglobin (7.2% versus 6.8%, P < .05), and cholesterol levels (6.3 versus 5.7 mmol/L, P < .0005) in women than men. In contrast, levels of fibrinogen (3.2 versus 3.1 g/L), tissue plasminogen activator antigen (10.6 versus 11.2 ng/mL), and von Willebrand factor (1.27 versus 1.23 IU/mL) were no different between women and men, respectively. These results suggest that elevated levels of plasminogen activator inhibitor-1 and factor VII:C may contribute to the increased cardiovascular risk of NIDDM that is particularly marked in women.
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PMID:Sex differences in coagulation and fibrinolysis in white subjects with non-insulin-dependent diabetes mellitus. 854 17

Tissue factor pathway inhibitor (TFPI), a kunitztype inhibitor of the extrinsic coagulation pathway, factor VII coagulant (FVIIc), FVIIa, and the fibrinolytic factors plasminogen activator inhibitor-1 (PA1-1) and tissue plasminogen activator (TPA) have been studied in various hyperlipidemias. Compared with a normal lipidic group, mean TFPI activity was 70% higher (P < .001) and 36% higher (P < .001) in type IIa and IIb hyperlipidemias, respectively, and was lower by 13% in type IV hyperlipidemia (P = .05). TFPI was correlated with LDL cholesterol (P < .001), total cholesterol (P < .001), HDL cholesterol (P < .01), apolipoproteins (apo) AI (P < .001) and B (P < .001) and lipoprotein a (P < .01). TFPI was negatively correlated with the triglyceride level (P < .05); the correlation was dependent on LDL cholesterol and HDL cholesterol levels, which were decreased in type IV hyperlipidemia. FVIIc activity (P < .001) was increased by 30% in both type IV and type IIb hyperlipidemia and was correlated with triglyceride levels. FVIIa was not significantly increased in any group compared with control group. FVIIc was correlated with triglyceride level (P < .001), while FVIIa was not. Interestingly, FVIIa was correlated with FVIIc (r = .5, P < .001) in the control group as well as in the hyperlipidemic groups (r = .32, P < .01). These results favor the hypothesis that higher FVIIc concentrations in hyperlipidemic patients are likely due to enhancement of synthesis of FVII and that a part of this FVII circulates in an activated chemical form. Compared with the control group, PAI-1 activity was twofold higher (P < .08) in type IIa hyperlipidemia, threefold higher (P < .001) in type IIb hyperlipidemia, and fourfold higher in type IV hyperlipidemia (P < .001). PAI-1 activity correlated with triglyceride levels (P < .001), apoB levels (P < .001) and total cholesterol levels (P < .05). These correlations were dependent on apoB and probably reflect the correlation between PAI-1 and VLDL. In contrast, TPA level was normal in the different hyperlipidemias. No correlation was found between TFPI, FVIIc, and PAI-1. Variation of TFPI activity appears to be related to the variations of its main lipoprotein carriers: LDL, HDL, and Lp (a). The association in hypertriglycemic patients of hypercoagulability (increased FVIIc and decreased TFPI) and hypofibrinolysis (increased PAI-1) may explain thrombosis predisposition of some of these patients. However, it would be interesting to study the increased levels of endothelium-derived TFPI in plasma induced by the injection of heparin.
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PMID:Levels of factor VIIc associated with decreased tissue factor pathway inhibitor and increased plasminogen activator inhibitor-1 in dyslipidemias. 854 30

Several haemostatic factors have been shown to have a predictive role in cardiovascular disease, although their relationship with prevalent peripheral arterial disease is not well reported. Using a random sample of 1592 men and women aged 55-74 years from Edinburgh, Scotland, we examined the relationship of von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and fibrin D-dimer antigens and factor VII activity to peripheral arterial disease. t-PA antigen and fibrin D-dimer showed significant linear trends of increased levels with increasing severity of disease in both sexes (p < or = 0.01) and vWF showed a similar pattern in men only (p < or = 0.01). On multivariate analysis, fibrin D-dimer was independently related to the risk of intermittent claudication (p < or = 0.01) and, among men, to the extent of arterial narrowing in the lower limb, as measured by the ankle brachial pressure index, (ABPI) (p < or = 0.001). These results are further evidence of a role for intravascular fibrin deposition in the development of peripheral atherosclerosis.
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PMID:Fibrin D-dimer, haemostatic factors and peripheral arterial disease. 857 5

In healthy nondiabetic women, oral contraceptives (OCs) affect hemostatic function. In diabetic women, there is concern that they may also increase the risk of diabetic vascular complications. This study was designed to examine the balance between coagulation activity and fibrinolytic activity--an indirect measure of endothelial cell function--in women with insulin-dependent diabetes mellitus (IDDM) during long-term use of OCs. The study group included 11 young women with uncomplicated IDDM who were prescribed ethinyl estradiol 30 micrograms and gestodene 75 micrograms. Twelve other diabetic women not taking OCs constituted the control group. Hemostatic function was evaluated at entry and after 1,3,6, and 12 months. In women taking OCs, plasma levels of factor VII(c) increased, while fibrinogen levels did not change. Inhibition of coagulation was affected by increased levels of protein C, although plasma levels of antithrombin III and protein S remained stable. The antigen concentrations of tissue-type plasminogen activator and plasminogen activator levels themselves were unchanged. There was a proportionate increase in the concentrations of thrombin-antithrombin III complexes and D-dimer. None of the hemostatic variables changed significantly in the control group. We conclude that the balance between coagulation activity and fibrnolysis does not change during use of this OC. Our findings suggest that low-dose OCs induce a procoagulatory state that is compensated for by enhanced fibrinolytic activity.
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PMID:Balance of coagulation activity with fibrinolysis during use of oral contraceptives in women with insulin-dependent diabetes mellitus. 857 52

We have compared the effects of partially hydrogenated fish oil (PHFO diet), partially hydrogenated soybean oil (PHSO diet), and butterfat (butter diet) on fibrinolytic and coagulation variables in 31 young men. The three test margarines, which contributed 78% of total fat in the diets, contained 70% butterfat, PHSO, or PHFO, each with 30% of soybean oil. Fat provided approximately 35% of energy, and the content of trans-fatty acids was 0.9%, 8.5%, and 8.0% of energy in the butter diet, PHSO diet, and PHFO diet, respectively. All diets contained 420 mg cholesterol per 10 megajoules per day. All subjects consumed all three test diets for 3 weeks, in a random order (crossover design). The PHSO diet resulted in higher levels of plasminogen activator inhibitor type 1 antigen and plasminogen activator inhibitor type 1 activity than the two other test diets. Fibrinogen increased on the butter diet compared with the PHFO diet. No significant differences in the levels of factor VII, fibrinopeptide A, D-dimer, tissue plasminogen activator or beta-thromboglobulin were observed between the three test diets. The PHFO and the PHSO diets have previously been shown to result in higher levels of Lp(a) compared with the butter diet. The present findings indicate that PHSO has unfavorable antifibrinolytic effects relative to PHFO and butter and that butter may be procoagulant relative to PHFO. More controlled studies are needed to assess definitely the impact of different hydrogenated fats on risk of coronary heart disease.
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PMID:Effects of partially hydrogenated fish oil, partially hydrogenated soybean oil, and butter on hemostatic variables in men. 863 Jun 62

The aim of the present study was to evaluate some metabolic, coagulation and fibrinolytic parameters in 35 patients (24 males and 11 females, mean age 57 +/- 4 years) suffering from myocardial infarction more than 6 months before with or without carotid atherosclerotic lesions. After evaluation by B-mode duplex scanning system of extracranial carotid arteries, the patients were subdivided into two groups: Group 1 (n = 16, with carotid plaques or intima-media thickening) and Group 2 (n = 19, without carotid plaques or intima-media thickening). Eighteen age- and sex-matched subjects were recruited as controls (Group 3). Groups 1 and 2 displayed significantly higher levels of total cholesterol and apolipoprotein B and significantly lower levels of HDL-cholesterol and apolipoprotein A1 than Group 3, while serum triglyceride and lipoprotein (a)-Lp (a) levels were significantly higher in Group 1 as compared to the control group. Moreover, Group 1 and 2 displayed significantly higher levels of factor VII, fibrinogen, F1+2, thrombin-antithrombin complex and plasminogen activator inhibitor (PAI) post venous occlusion and significantly lower levels of tissue plasminogen activator (t-PA) post venous occlusion than Group 3. Significantly higher levels of t-PA and PAI pre venous occlusion and significantly lower levels of antithrombin III, C-protein and S-protein were observed in Group 1 as compared to controls. In patients with highest Lp(a) level, the lowest t-PA level post venous occlusion and the highest PAI level post venous occlusion were observed. Our data show an activation of coagulation and a deficient fibrinolysis in survivors of myocardial infarction, particularly in those with associated carotid atherosclerotic lesions. We speculate that this thrombophilic state may play a key role in the pathogenesis of atherosclerotic vascular disease and thromboembolic complications.
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PMID:[Thrombophilic state inpatients suffering from myocardial infarction with or without carotid atherosclerotic lesions]. 870 61

Fibrinolysis and coagulation were studied in 10 neonates undergoing cardiac operations for congenital heart defects. Coagulation was activated during cardiopulmonary bypass as evidenced by highly increased prothrombin fragment 1 + 2 levels compared with preoperative values. Prothrombin fragment 1 + 2 levels remained elevated until postoperative day 3. Unlike coagulation, fibrinolysis was not activated during cardiopulmonary bypass but did show late activation on postoperative day 3, as evidenced by elevated levels of the fibrin degradation product D-dimer. Lack of fibrinolytic activation during bypass and its appearance on postoperative day 3 were partly explained by changes observed in tissue plasminogen activator and its inhibitor. During bypass, levels of tissue plasminogen activator and its inhibitor increased by 3.4-fold and 3.2-fold, respectively. In the postoperative period, levels of plasminogen activator inhibitor normalized rapidly whereas tissue plasminogen activator remained elevated, resulting in late fibrinolytic activation on postoperative day 3. In accordance with elevated prothrombin fragment 1 + 2, platelet count, antithrombin III, protein C, prothrombin, and factor VII were decreased on postoperative day 2, indicating ongoing consumptive coagulopathy. Nine patients had antithrombin III and six had protein C levels below age-specific normal ranges, consistent with an acquired deficiency state. Three had central venous thrombosis by postoperative day 4 or 5. In all three, thrombosis was preceded by antithrombin III deficiency, protein C deficiency, and highly elevated plasminogen activator inhibitor (3.7 to 37 times the mean of the other patients) on postoperative days 1 to 3. In conclusion, cardiopulmonary bypass in neonates caused rapid and profound alterations in the coagulation and fibrinolytic systems and initiated consumptive coagulopathy lasting until at least postoperative day 3. Thrombophilic abnormalities in antithrombin III, protein C, and fibrinolysis were frequently found and were associated with serious thrombotic complications.
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PMID:Fibrinolysis, antithrombin III, and protein C in neonates during cardiac operations. 880 Jan 54

The relationship between liver steatosis, evaluated by ultrasonography, and various plasma haemostatic factors was examined in 64 apparently healthy males, aged 38 years. Plasma levels of factor VII clotting activity (F-VIIc), plasminogen activator inhibitor-1 (PAI-1) activity and antigen, tissue-type plasminogen activator (t-PA) activity significantly differed in men with liver steatosis (n = 31) as compared with those without steatosis (n = 33). No significant differences were found in t-PA antigen and F-VII antigen. The men with liver steatosis also had significantly higher body mass index (BMI), plasma triglyceride and 2 h post-load insulin concentrations. While the differences in plasma haemostatic factors were substantially unchanged after adjustment for BMI, they totally disappeared when further allowance was made for plasma triglyceride and 2 h insulin concentrations. In conclusion, these results indicate that liver steatosis correlates specifically with increased PAI-1, F-VIIc and decreased t-PA levels, and suggest that such a relation is largely mediated by concomitant alterations in plasma triglyceride and insulin concentrations.
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PMID:Liver steatosis and its relation to plasma haemostatic factors in apparently healthy men--role of the metabolic syndrome. 881 54

Disturbances of the haemostatic system may favour the development of vascular damage and the final occlusion events in the progress of coronary heart disease (CHD). It has been shown recently in epidemiological studies, that increased concentration of several factors, mainly fibrinogen, factor VII, von Willebrand factor (vWF), and the fibrinolytic variables plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA), can be considered as risk factors for CHD. As morbidity and mortality through coronary atherosclerosis are higher in type 2 diabetic patients than in nondiabetic subjects and as insulin resistance represents a situation which favours the development of atherothrombosis, evaluation of the haemostatic factors which are recognized as risk factors may be interesting to consider in these situations. In fact, it has been shown that the fibrinolytic parameters PAI-1 and t-PA antigen are strongly related to the metabolic disorder of insulin resistance, whereas the link with fibrinogen, factor VII, and vWF remains weak. Many cross-sectional studies conducted in different populations have shown that PAI-1 and t-PA antigen (which represents t-PA/PAI-1 complexes) are strongly correlated with insulin, triglyceride, high-density lipoprotein (HDL) cholesterol, body mass index, walst-to-hip ratio and blood pressure, and that the improvement of insulin resistance improves in parallel the metabolic abnormalities and the concentration of the fibrinolytic parameters. Attempts at explaining the elevated PAI-1 and t-PA antigen levels in the insulin resistance syndrome have involved many clinical and in vitro studies, in which the role of insulin, insulin propeptides, very-low-density lipoprotein (VLDL) triglyceride, insulin resistance per se, glucose, and adipose tissue have successively been analysed and the main results of these studies are presented in this review. Due to recent experimental data from animal models of thrombosis, a pathogenic role of decreased fibrinolytic activity or increased PAI-1 levels can be proposed and could play a role in the development of vascular disease in subjects with Type 2 diabetes or insulin resistance.
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PMID:Thrombogenic and fibrinolytic factors and cardiovascular risk in non-insulin-dependent diabetes mellitus. 886 93


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