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)

A high intake of beta-carotene has been associated with a decreased risk for cardiovascular disease. To evaluate whether beta-carotene may exert a protective effect through an impact on haemostasis a randomized, placebo-controlled trial was conducted in male smokers (n = 149) using 20 mg/day beta-carotene for 14 weeks. For comparisons, haemostatic indicators were also evaluated in a group of non-smokers (n = 54). Smokers compared with non-smokers had higher fibrinogen (3.5 vs. 3.1 mg/ml, P < 0.01), higher tissue-type plasminogen activator antigen (t-PA; 8.03 vs. 6.60 ng/ml, P < 0.05), lower levels of soluble fibrin (3.40 vs. 5.16 micrograms/ml, P < 0.01) and slightly higher plasma levels of total degradation products of fibrin and fibrinogen (TDP; 47.0 vs. 41.3 ng/ml, P = 0.21). Within the group of smokers, there were no initial differences in the four haemostatic indicators between the placebo (n = 77) and beta-carotene (n = 72) groups, and in both groups there was virtually no change in the indicators during the 14 weeks treatment. It is concluded that the different haemostatic profile in smokers may partly explain their increased risk for cardiovascular disease. beta-Carotene has no influence on the measured haemostatic indicators, and cardiovascular protection for beta-carotene via a beneficial effect on haemostasis seems improbable.
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PMID:No influence of beta-carotene on haemostatic balance in healthy male smokers. 779 55

Epidemiological studies have provided evidence that attenuated fibrinolytic activity and increased antigen levels of plasminogen activator are risk factors for coronary heart disease (CHD). In a comparative study, tissue plasminogen activator (t-PA) antigen and activity concentrations were examined in plasma from familial hypercholesterolaemia (FH) patients without manifest CHD (n = 14) and in age- and sex-matched normolipaemic controls (NLC) at rest and after the same bicycle exercise. The FH patients had higher systolic and diastolic blood pressure than their controls. The plasma level of t-PA antigen was higher in FH patients than in NLC under basal conditions (7.3 +/- 3.1 ng/ml vs 4.8 +/- 2.2 ng/ml, P = 0.022), whereas no difference was found in t-PA activity. Bicycle exercise induced a marked increase in t-PA antigen (P < 0.001 for both groups) which did not differ between groups. A more prominent rise in t-PA activity was observed among the FH patients during the exercise (1.71 +/- 0.99 vs 0.85 +/- 0.89 IU/ml, P = 0.24). Neither the basal level of thrombin-antithrombin III complex (TAT) nor the significant increase (P < 0.001 for both groups) induced by exercise differed between groups. A high t-PA antigen level may precede clinical manifestations of cardiovascular disease in patients with familial hypercholesterolaemia.
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PMID:Basal plasma concentration of tissue plasminogen activator (t-PA) and the adaption to strenuous exercise in familial hypercholesterolaemia (FH). 786 85

Recently waist/hip ratio (WHR), a marker of body fat distribution, has been described as a risk factor for cardiovascular disease (CVD). The aim of the present study was to evaluate the influence of body fat distribution on metabolic, haemostatic and haemorheological pattern in premenopausal obese women with different WHR. Fourty premenopausal obese women were subdivided into two groups, matched for age and body mass index (BMI): 20 women with abdominal obesity (WHR = 0.94 +/- 0.02) and 20 women with peripheral obesity (WHR = 0.77 +/- 0.03). Twenty nonobese women were recruited as control group. The abdominal obesity group had significantly higher blood glucose, triglycerides, total cholesterol, Apolipoprotein B and plasma insulin levels and lower high density lipoprotein (HDL) cholesterol and Apolipoprotein A1 levels than the control group. All the haemostatic (figrinogen, Factor VII, plasminogen activator inhibitor (PAI) activity and tissue plasminogen activator (t-PA) antigen (Ag) pre venous occlusion (VO)) and haemorheological parameters (haematocrit, whole blood filterability, blood and plasma viscosity) were significantly higher in the abdominal obesity group as compared to the control group. In contrast, mean values of t-PA (Ag) post VO were significantly lower in abdominal obese women. Moreover positive correlations between WHR and plasma insulin (r = 0.68, p < 0.05), between WHR and fibrinogen (r = 0.63, p < 0.05) and between WHR and PAI pre VO (r = 0.71, p < 0.05) and a negative correlation between WHR and t-PA (Ag) post VO (r = -0.55, p < 0.05) were found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coagulation, fibrinolysis and haemorheology in premenopausal obese women with different body fat distribution. 799 33

Radioactively labeled human fibrin clots were placed into veins of Macaca arctoides monkeys. Thrombolysis was recorded by the disappearance of radioactivity and by angiography. Streptokinase (SK) and urokinase (UK) induced thrombolysis was potentiated by low dose aspirin (ASA) and pentoxifylline (PE). Studies on the mechanisms of action revealed that PE inhibits platelet aggregation, releases tissue plasminogen activator (t-PA) from the endothelium, increases red cell deformability and inhibits white cell adhesion. Thrombolysis by pro-urokinase (pro-UK) was potentiated by low dose SK probably because of streptokinase-plasmin activation of pro-UK to UK. Platelet aggregation inhibitory effects, disaggregation of platelet aggregate inducing effects, and the t-PA releasing activity of PE was demonstrated in patients with obstructive cardiovascular disease. Pharmacodynamic studies suggested that PE metabolites one and five are most effective from this point of view. These metabolites are currently studied in combination with thrombolytic enzymes.
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PMID:Potentiation of thrombolytic therapy by enzyme combinations and with aspirin or pentoxifylline. 799 60

Endogenous tissue-type plasminogen activator (tPA) has been hypothesised to be a marker of baseline fibrinolytic capacity. We therefore tested whether tPA antigen is associated with the occurrence of future myocardial infarction (MI) among apparently healthy individuals. tPA antigen concentrations were measured at baseline in plasma samples from 231 apparently healthy men from the Physicians' Health Study cohort who later developed MI, and in an equal number of controls matched for age and smoking habit who remained free of reported cardiovascular disease during a follow-up of 60.2 months. In crude matched-pair analyses, baseline concentrations of tPA antigen were higher in cases than controls (p = 0.03) and strongly associated with risk of future MI. Specifically, the relative risks of developing a first MI from lowest (referent) to highest quintiles of tPA antigen were 1.00, 1.27, 1.75, 1.88, and 2.81 (p for trend 0.0008, 95% CI for the relative risk in the fifth as compared with first quintile 1.47 to 5.37, p = 0.002). Analyses which adjusted for risk factors that affect progression of atherosclerosis, particularly HDL-cholesterol, abolished the statistical significance of this association, a finding which suggests that elevations of tPA antigen are a result rather than a cause of atherosclerotic coronary disease. These prospective data suggest that endogenous tPA concentrations increase as a consequence of important preclinical atherosclerosis and therefore may be a marker for risk of future MI.
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PMID:Endogenous tissue-type plasminogen activator and risk of myocardial infarction. 810 Mar 14

The first generation high-dose ( 80 mcg estrogen) oral contraceptives (OCs) were associated with an increased risk of deep venous thrombosis (DVT). So manufacturers removed the high-dose OCs and first replaced them with OCs with 50 mcg estrogen, resulting in a lower incidence of thromboembolic events (40 vs. 20/100,000 users). When they introduced an even lower dose OC (30 mcg estrogen), the incidence fell further (about 8/100,000 users). Yet, women using the lowest-dose OCs still have DVT more often than do control women. Life-style, age, and smoking may be confounding factors, however. It is not clear whether loss of endogenous ovarian steroid production or the effects of the orally administered contraceptive steroids cause significant changes in hemostatic factors (antithrombin III, protein S, protein C, plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor 1, histidine-rich glycoprotein, and VII, VIII, X, XII coagulation factors) during OC use. These changes tend to be within normal ranges. There is some doubt that these changes have any clinical significance. In nonsmokers, increased activity of anticoagulant factors and fibrinolytic factors counteract the effects on coagulation factors. Progestin-only OCs appear to affect hemostasis but have not increased the risk of thrombosis. There are considerable differences between people in pharmacokinetics and pharmacodynamics of contraceptive steroids. These differences may account for the increased risk of thromboembolic events in some people. Further research should identify methods of individualizing the dose of contraceptive steroids for a single patient. It should also explore the close interrelationship between hemostasis and lipid metabolism, carbohydrate metabolism, and hypertension in the development of cardiovascular disease in OC users. Providers should discourage women with a past history of DVT from using hormonal contraception.
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PMID:Coagulation and anticoagulation effects of contraceptive steroids. 817 1

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

High plasma levels of lipoprotein(a) [Lp(a)] are considered to be an independent risk factor for premature cardiovascular disease and are inversely associated with apolipoprotein(a) [apo(a)] isoform sizes. The contribution of apo(a) polymorphism to the inhibition of fibrinolysis, a mechanism that may favor thrombus development, was therefore evaluated by measuring the ability of Lp(a) particles of distinct apo(a) isoform content to compete with plasminogen for fibrin binding during plasminogen activation by fibrin-bound tissue-type plasminogen activator. The rate of plasmin generation was most efficiently inhibited by an isoform with a molecular weight (M(r)) of approximately 540 Kd. An isoform with M(r) approximately 590 Kd produced a less pronounced effect, whereas the isoform with M(r) approximately 610 Kd failed to inhibit plasminogen activation. These effects were directly proportional to the amount of Lp(a) bound to the carboxy-terminal lysine residues of degraded fibrin. The relative affinity of the binding (kd range, 16 to 180 nmol/L) reflected the ability of individual Lp(a) isoforms to inhibit the binding of plasminogen (kd, 600 nmol/L). The question of the influence of kringle sequence variability on the binding to fibrin was not addressed by the present work. These data suggest that apo(a) isoform types with high affinity for fibrin may influence the ability of Lp(a) to interfere with fibrinolysis and contribute thereby to the association of elevated levels of Lp(a) with atherosclerotic and thrombotic risks.
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PMID:Does apolipoprotein(a) heterogeneity influence lipoprotein(a) effects on fibrinolysis? 832 99

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

The passage of the menopause has been reported to be followed by a steadily increasing risk of cardiovascular disease (CVD). Changes in the concentrations of certain coagulation factors and fibrinolytic components are considered risk factors for CVD. We evaluated the differences in some of these variables between a premenopausal group (A) (n = 28) and two postmenopausal groups, one of women less than 18 months past the menopause (B) (n = 28), the other of women more than 18 months past the menopause (C) (n = 21). The variables measured were serum oestradiol content, plasma antithrombin III (AT III) activity, protein C activity and the plasma concentrations of tissue type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI-1) antigen, and fibrinogen. As compared with the premenopausal women (group A), group C showed significantly higher values for AT III and protein C activity and for t-PA and PAI-1 antigen; and group B and C both showed significantly higher fibrinogen concentrations. This probably means that haemostatic balance was maintained in the postmenopausal women, although the increased concentrations of fibrinogen and PAI-1 might constitute risk factors for the development of cardiovascular disease.
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PMID:Passage of the menopause is followed by haemostatic changes. 841 39


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