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

A slightly elevated urinary albumin excretion rate (UAER), above 5-10 microgram/min, is a predictor of atherosclerotic cardiovascular disease. Endothelial dysfunction is an important early feature of atherosclerosis. The plasma concentration of von Willebrand factor (vWF), a potential marker of endothelial dysfunction, predicts a subsequent increase of UAER in patients with diabetes. The aim of this study is to test the hypothesis that high concentrations of vWF as well as other haemostatic factors predict progression of UAER in clinically healthy subjects. UAER was measured together with selected markers of haemostatic function-vWF, tissue plasminogen activator (tPA), plasminogen activator inhibitor, factor VII and fibrinogen-in healthy volunteers aged 40-65 years. After a mean follow-up of 4.1 years, 64 of 74 agreed to a re-examination including re-measurement of UAER. Baseline vWF and tPA were both positively correlated to the change in UAER during follow-up (r=0.26, P=0.04 and r=0.40, P=0.001 respectively). The mean UAER increased significantly by 7.6 microgram/min and 7.5 microgram/min respectively in subjects with vWF and tPA above the medians at baseline (P=0.01 and P=0.003 respectively), whereas no changes in UAER were seen in subjects with vWF and tPA below the medians. Subjects with high tPA were also characterized by an excess of other cardiovascular risk factors at baseline. No significant differences in these risk factors were present between subjects with high or low vWF. High plasma concentrations of vWF and tPA are associated with progression of UAER in clinically healthy subjects. Both vWF and tPA are secreted by endothelial cells and the results suggest that endothelial dysfunction leads to progression of UAER.
 ...
PMID:Endothelial haemostatic factors are associated with progression of urinary albumin excretion in clinically healthy subjects: a 4-year prospective study. 1036 4

Although coronary bypass graft surgery has increased the survival and quality of life of many individuals, patients remain at risk of restenosis and thrombotic occlusion of the coronary arteries and bypass grafts. In the screening period for participation in the multicenter Post Coronary Artery Bypass Graft (Post CABG) trial, the effects of 1 mg daily warfarin were evaluated using paired patient samples collected prior to and after at least 21 days of treatment. In stable patients (n = 40; 39 males 1 female; 51-74 years old) who previously had undergone coronary artery revascularization (1-10 years), no alterations in prothrombin time, international normalized ratio (INR), prothrombin fragment 1.2, or the hemostatic risk factors factor VII antigen and coagulant activity, von Willebrand's factor, fibrinogen, tPA, or PAI-1 were associated with the 1 mg daily warfarin treatment. The observations reported here supported the Post CABG Studies Steering Committee decision to treat patients with 1-4 mg warfarin daily adjusted to achieve INRs not to exceed 2. 0 consistent with low-intensity therapy.
 ...
PMID:Hemostatic effects of 1 mg daily warfarin on post CABG patients. Post CABG Studies Investigators. 1037 14

Thrombus formation at the site of atherosclerotic lesions, especially on a ruptured plaque, plays a central role in the "atherothrombosis" hypothesis. An activation of the hemostasis and a disturbed fibrinolysis are known. These alterations are especially marked in patients with acute coronary syndromes. In stable coronary artery disease, fibrinogen is elevated. Furthermore, minor alterations of the contact phase factor VII and consecutively of the thrombin system are detectable depending on the study population. Thrombin generation and activation become marked in patients with unstable angina pectoris or acute myocardial infarction. Possible reasons for this activation are an activation of the contact phase factor XII system and the release of tissue factor both from the ruptured plaque and from stimulated monocytes. The fibrinolytic system is markedly altered already in patients with stable coronary heart disease. Increased levels of tissue-type plasminogen activator and of urokinase-type plasminogen activator/receptor are measurable in atheromas. Tissue-type plasminogen activator mass concentration is systemically elevated already at early stages of atherosclerosis. Especially in patients with increased risk for acute coronary syndromes, the plasminogen activator inhibitor activity is significantly increased. Furthermore, a hypercoagulative state with increased d-dimer levels and plasmin-antiplasmin complexes can be measured. The alterations of hemostasis and especially of fibrinolysis are detectable for prolonged time period and persist much longer than the clinical symptoms of the patients. The increased plasminogen activator inhibitor activity is associated with the metabolic syndrome and constitutes an (in part genetically determined) disturbance in patients with stable or unstable coronary heart disease. However, the large intra- und interobserver as well as diurnal variability of this marker limits its use as a routine measure for risk stratification in patients. Alterations of the hemostasis and disturbances of fibrinolysis are detectable during the chronic as well as the acute phase of atherosclerosis. These changes are best documented for coronary heart disease, whereas less data are available for other manifestations of atherosclerosis. The use of newly developed molecular markers for single reaction steps of pathways instead of global functional tests and of new molecular biological methods did considerably improve the detailed knowledge on the pathomechanisms of the development of atherosclerosis, making the development of targeted therapies, e.g., against receptors possible. Future studies will investigate the quantitative impact of the various activated pathways (cause or reaction) and the effects of interventions on these pathomechanisms in patients with acute coronary syndromes. Studies will have to focus especially on the meaning of polymorphisms, early changes in the development of atherosclerosis and interactions with inflammatory processes.
 ...
PMID:[Blood coagulation and fibrinolysis in arteriosclerosis]. 1041 53

Hemodialysis (HD) patients have accelerated cardiovascular morbidity and mortality rates compared with the general population. Identifying the factors that predict major coronary events in this population can direct the focus on prevention. This cross-sectional study compares known and suspected cardiovascular risk factors in HD patients with and without prevalent cardiovascular disease (CVD). In 76 HD patients (prevalent CVD, 44 of 76 patients), serum lipid, lipoprotein, apolipoprotein (Apo), plasma fibrinogen, tissue plasminogen activator (TPA), plasminogen activator inhibitor (PAI-1), and factor VII levels were measured using standard kits. Serum malondialdehyde (MDA; a marker of oxidative stress) was measured using spectrophotometry. Predictor variables were compared using analysis of variance and chi-squared tests, as appropriate. CVD prevalence was modeled using multiple logistic regression analysis, and odds ratios (OR) were calculated. Serum lipid, lipoprotein, Apo, plasma TPA, PAI-1, and factor VII values did not differ significantly from laboratory norms or discriminate for prevalent CVD in HD patients. Plasma fibrinogen levels were significantly elevated in HD patients compared with laboratory norms (369.4 +/- 130.02 v 276.7 +/- 77.7 mg/dL; P < 0.0001) but were not significantly different in HD patients with and without prevalent CVD. Serum MDA levels, both before and after the midweek HD treatment, were significantly elevated in all HD patients compared with laboratory norms (pretreatment, 2.6 +/- 0.8 nmol/mL; posttreatment, 2.1 +/- 0.3 v 0.91 +/- 0.09 nmol/mL; P < 0.01) and were significantly elevated in HD patients with prevalent CVD versus those without (pretreatment, 2.8 +/- 0.6 v 2.4 +/- 0.4 nmol/mL; P < 0.01; posttreatment, 2.3 +/- 0.4 v 1.94 +/- 0.2 nmol/mL; P < 0.01). Only serum MDA levels, both before and after the midweek treatment, contributed to the explanation of variation in CVD prevalence. OR for CVD in the highest versus lowest tertile of pretreatment MDA level was 2.71 (95% confidence interval [CI], 1.42 to 5.19). ORs for CVD in the highest versus lowest tertile of posttreatment MDA level was 3.65 (95% CI, 1.6 to 8.32).
 ...
PMID:Comparison of hemostatic factors and serum malondialdehyde as predictive factors for cardiovascular disease in hemodialysis patients. 1046 53

The aim of the present study was to evaluate metabolic, coagulation and fibrinolytic parameters in 45 patients [31 men, 14 women, aged 56.5 +/- 3.5 years (mean +/- SD)] who had suffered myocardial infarction more than 6 months earlier, with or without carotid atherosclerotic lesions. After the extracranial carotid arteries had been evaluated using a B-mode Duplex scanning system, patients were subdivided into two groups: group 1 (n = 20) with carotid plaques or measurable intima-media thickness; and group 2 (n = 25) without carotid plaques or measurable intima-media thickness. Twenty-two age- and sex-matched subjects were recruited as controls (group 3). Groups 1 and 2 displayed significantly higher levels of total cholesterol, apolipoprotein B, human autoantibodies against oxidised low-density lipoprotein and the c fraction of the third component system, and significantly lower levels of high-density lipoprotein cholesterol and apolipoprotein A1 than group 3. However, serum levels of triglyceride and lipoprotein (a) were significantly higher in group 1 than in the control group. Moreover, groups 1 and 2 displayed significantly higher levels of factor VII, fibrinogen, fragment 1+2, thrombin-antithrombin complex and plasminogen activator inhibitor after venous occlusion, and significantly lower levels of tissue-type plasminogen activator after venous occlusion than group 3. Significantly higher levels of tissue-type plasminogen activator and plasminogen activator inhibitor before venous occlusion were observed in groups 1 and 2 and significantly lower levels of antithrombin III, protein C and protein S were observed in group 1 compared with the controls. Patients were also analysed according to levels of lipoprotein (a). The lowest levels of tissue-type plasminogen activator after venous occlusion and the highest levels fragment 1 + 2, the c fraction of the third component system, and plasminogen activator inhibitor after venous occlusion were observed in patients with the highest levels of lipoprotein (a). Our data demonstrate an activation of coagulation and 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.
 ...
PMID:Elevated levels of lipoprotein (a) in patients suffering from myocardial infarction with carotid atherosclerotic lesions. 1049 14

Do extremely old persons have a genetically favourable profile which has protected them from cardiovascular death? We have tried to answer this question by measuring DNA polymorphisms of selected cardiovascular risk indicators [factor VII, FVII (R/Q353, intron 7 (37bp)n, and -323ins10), beta fibrinogen (-455G/A), plasminogen activator inhibitor type 1, PAI-1 (-675(4G/5G)), tissue plasminogen activator, t-PA (intron 8 ins311), platelet receptor glycoprotein IIb/IIIa, GPIIb/IIIa (L/P33), prothrombin (20210G/A), methylene tetrahydrofolate reductase, MTHFR (A/V114), angiotensin converting enzyme, ACE (intron 16 ins287), and angiotensinogen (M/T235)]. Blood was collected from 187 unselected Danish centenarians, and 201 healthy Danish blood donors, aged 20-64 years (mean age 42 years). Genomic DNA was amplified using PCR and the genotype was determined by RFLP methods or allele-specific amplification followed by agarose gel electrophoresis. The frequencies of the high-risk alleles in centenarians were: for FVII R/Q353 0.91; for FVII intron 7 (37bp)n 0.67; for FVII-323 ins10 0.90; for fibrinogen 0.16; for PAI-1 0.52; for t-PA 0.59; for GPIIb/IIIa 0.16; for prothrombin 0.008; for MTHFR 0.33; for ACE 0.52; and for angiotensinogen 0.36. Comparable frequencies were observed in the blood donors. Subgroup analysis of men and women separately gave similar results. The genotype frequencies in the centenarians and the blood donors were similar for all polymorphisms, and this study suggests that common variations in genes associated with cardiovascular risk do not contribute significantly to longevity.
 ...
PMID:Longevity is independent of common variations in genes associated with cardiovascular risk. 1049 71

Among users of low-dose oral contraceptives (OC), cardiovascular diseases occur mainly in smokers. The mechanisms by which OC and smoking increase the risk for arterial thrombotic risk have not been adequately explained. Epidemiological evidence suggests that changes in blood coagulation and fibrinolysis may play an important role as determinants of thrombotic events. Therefore, we have investigated the associations of OC and smoking with haemostatic variables among 194 premenopausal healthy women. Fourty women were current users of low-dose OC and 62 women were smokers. After adjustment for age and body mass index, mean values of factor XIIa, factor VII activity and antigen, fibrinogen, D-dimer, global fibrinolytic capacity were significantly higher in OC users than in non-users. Mean levels of PAI activity and t-PA antigen were significantly lower in OC users than in non-users. Smokers had significantly higher mean values of fibrinogen than non-smokers. Two-way analysis of variance showed that the differences in mean levels of fibrinogen and D-dimer between OC users and non users were restricted to smokers. The positive and significant interactions between OC use and smoking in their effects on haemostatic variables were consistent with respect to age and type of OC. These preliminary data suggest that elevated plasma levels of fibrinogen and intravascular fibrin deposition may play a role in the pathogenesis of arterial thrombotic disease among women who are both low-dose OC users and smokers.
 ...
PMID:Elevated plasma fibrinogen and increased fibrin turnover among healthy women who both smoke and use low-dose oral contraceptives--a preliminary report. 1049 73

The effects of fluvastatin therapy on parameters of coagulation and fibrinolysis were evaluated in patients with diabetic dyslipidemia in a randomized, placebo-controlled study. Fluvastatin therapy was associated with a small reduction in factor VII coagulant activity, von Willebrand factor, and in plasminogen activator inhibitor 1 and tissue plasminogen activator antigens, but the effects of fluvastatin on hemostatic factors were much less marked than its effects on plasma lipids.
 ...
PMID:Effects of fluvastatin on prothrombotic and fibrinolytic factors in type 2 diabetes mellitus. 1053 16

Data on the effect of hormone replacement therapy on hemostasis are inconsistent, and there are few data in women with coronary artery disease. In a single-center, open, randomized study, 118 postmenopausal women with angiographically verified coronary artery disease were randomized to hormone replacement therapy, given as long-cycle transdermal 17-beta-estradiol (50 microg/24 hour) for 3 months with sequential medroxy-progesterone acetate for 14 days, or to a control group receiving no therapy. Hemostatic parameters were measured at baseline and after 3 and 12 months of therapy. The coagulation inhibitors antithrombin, protein C, and protein S, but not tissue factor pathway inhibitor, decreased significantly from baseline in the hormone replacement therapy group at both 3 and 12 months as compared with the control group. The absolute decreases within the hormone replacement therapy group were 3 to 10%. No significant differences between the two treatment groups were observed for the coagulation products prothrombin fragment 1+2 or thrombin-antithrombin complex or for D-dimer, although there were significant decreases in the levels within the hormone replacement therapy group. Levels of fibrinogen, activated factor VII, and factor VII antigen were not significantly influenced by hormone replacement therapy treatment. Similarly, nonsignificant changes were detected for the fibrinolytic parameters tissue plasminogen activator activity, tissue plasminogen activator antigen, and global fibrinolytic activity, but plasminogen activator inhibitor type 1 was significantly lower in the hormone replacement therapy group due to a questionable increase in the levels in the control group. In conclusion, treatment with transdermal estradiol combined with long-cycle progestins was associated with no net activation of coagulation despite reduced levels of coagulation inhibitors.
 ...
PMID:The effects of hormone replacement therapy on hemostatic variables in women with angiographically verified coronary artery disease: results from the estrogen in women with atherosclerosis study. 1070 30

It has been suggested that milk fat, due to its content of saturated fatty acids, may have a thrombogenic effect. In the present study the fatty acid profile of milk fat was modified by changing the feeding regimens of cows and the effect on haemostatic variables of a diet containing the modified milk fat (M) was compared with that of a diet containing milk fat of typical Danish composition (D). In the modified fat 16% of the saturated fatty acid (C12-C16) content was replaced mainly by oleic acid. Eighteen subjects were fed on two strictly controlled isoenergetic diets containing 40% energy from total fat (30% energy from the test fats) for periods of 4 weeks in a study with a crossover design. Fasting samples were taken in the last week of each study period. Postprandial samples were taken on day 21, 3 h after lunch (n 18), and on the last day of the study 2, 4, 6 and 8 h after a fat load containing 1.2 g of one of the milk fats/kg body weight (n 8). After 4 weeks' dietary intervention fasting plasma factor VII coagulant (FVIIc) activity, tissue-type plasminogen activator (t-PA) activity, plasminogen activator inhibitor (PAI-1) antigen and beta-thromboglobulin did not differ between diets M and D. Postprandially FVIIc and t-PA activities increased (P < 0.001) and PAI-1 antigen and PAI-1 activity decreased (P < 0.001) as compared with fasting values, regardless of diet. After the fat load, the postprandial increase in FVIIc was marginally lower after diet M than diet D (diet effect, P < 0.05). In conclusion, the modified milk fat obtained by the applied feeding strategy had virtually the same effects on haemostatic variables as conventional milk fat.
 ...
PMID:Effect of modified dairy fat on fasting and postprandial haemostatic variables in healthy young men. 1074 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>