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)

Utilization of angiography after acute myocardial infarction (AMI) treated with thrombolytics has been shown in large clinical trials to be related primarily to the availability of the procedure and not individual clinical circumstances. This study evaluated the regional influence of overall population cardiovascular mortality on utilization of angiography in the United States participants of the Global Utilization of Streptokinase and t-PA for Occluded Arteries (GUSTO-1) trial. Published summary statistics from GUSTO-1 and U.S. Census Bureau 1991 data were evaluated using simple and multiple linear regression with analysis for outliers. Region predictor variables (age adjusted) included mean total cardiovascular deaths/100,000/year (ICD/9 codes 390 to 459), mean coronary artery disease deaths/ 100,000/year (ICD/9 codes 410 to 414), and mean stroke deaths/100,000/year (ICD/9 codes 430 to 438), with the major outcome being regional proportion of GUSTO-1 patients undergoing angiography during the hospital stay after treatment with thrombolysis. All 3 cardiovascular death rates varied significantly by region (p < 0.00002) with no significant difference in GUSTO-1 mortality by region (p = 0.25). Simple linear regression analysis revealed associations between regional death rates and angiography use (r = 0.60, p = 0.12; r = 0.39, p = 0.33; r = 0.81, and p = 0.015). Multiple stepwise linear regression analysis found regional death rate due to stroke as the strongest predictor of angiography use with 65.86% of the variation explained by the model. New England was found to be a consistent outlier with reduced angiography use because of its background regional disease burden. This study confirms regional bias in the use of angiography in GUSTO-1. This form of operator bias appears to be due to more aggressive practice patterns in regions, except New England, where the overall cardiovascular disease burden is greater in terms of lives lost per 100,000 per year.
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PMID:Influence of regional cardiovascular mortality on the use of angiography after acute myocardial infarction. 906 11

In recent years, a prodigious amount of information has been gathered regarding the relationship between vascular biology and the mechanisms underlying cardiovascular disease. Activation of elements of the reninangiotensin system (RAS) appear to play an important role in the development and progression of conditions such as hypertension, coronary artery disease, and heart failure. Indeed, converging lines of evidence indicate that angiotensin-converting enzyme (ACE) regulates a delicate balance among a multitude of factors responsible for vascular tone, cellular growth promotion and inhibition, and pro- and anti-inflammatory effects. Because angiotensin II inhibits fibronectin, stimulates expression of plasminogen activator inhibitors, and degrades bradykinin, thereby impairing production of nitric oxide, ACE and the RAS are also involved in thrombosis and fibrinolysis. The favorable effects of ACE inhibition on endothelial function and, potentially, on cardiovascular morbidity and mortality are believed to result not only from angiotensin II suppression but also its consequent bradykinin preservation and nitric oxide production.
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PMID:The integrated effects of angiotensin II. 912 15

Oestrogen replacement therapy is associated with a decreased risk of cardiovascular disease in postmenopausal women. Patients with non-insulin-dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk. However, oestrogen replacement therapy is only reluctantly prescribed for patients with NIDDM. In a double blind randomized placebo controlled trial we assessed the effect of oral 17 beta-estradiol during 6 weeks in 40 postmenopausal women with NIDDM. Glycated haemoglobin (HbA1c), insulin sensitivity, suppressibility of hepatic glucose production, lipoprotein profile and parameters of fibrinolysis were determined. The oestrogen treated group demonstrated a significant decrease of HbA1c and in the normotriglyceridaemic group a significantly increased suppression of hepatic glucose production by insulin. Whole body glucose uptake and concentrations of non-esterified fatty acids did not change. LDL-cholesterol- and apolipoprotein B levels decreased, and HDL-cholesterol, its subfraction HDL2-cholesterol and apolipotrotein A1 increased. The plasma triglyceride level remained similar in both groups. Both the concentration of plasminogen activator inhibitor-1 antigen and its active subfraction decreased. Tissue type plasminogen activator activity increased significantly only in the normotriglyceridaemic group. Oestrogen replacement therapy improves insulin sensitivity in liver, glycaemic control, lipoprotein profile and fibrinolysis in postmenopausal women with NIDDM. For a definite answer as to whether oestrogens can be more liberally used in NIDDM patients, long term studies including the effect of progestogens are necessary.
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PMID:Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM. 924 7

An Alu-repeat polymorphism in the gene coding for tissue-type plasminogen activator has been described recently, and it has been hypothesized that this polymorphism may predict risk of coronary thrombosis. In a prospective cohort of nearly 15,000 apparently healthy men, presence of an Alu-repeat insertion/deletion (I/D) polymorphism in the gene coding for tissue-type plasminogen activator was determined among 369 study participants who subsequently suffered a first myocardial infarction (cases) and among a group of 369 age- and smoking-matched study participants who remained free of reported cardiovascular disease during follow-up (controls). The distributions of the II, DI, and DD genotypes of the tissue-type plasminogen activator polymorphism among men who subsequently suffered myocardial infarction (0.30, 0.50, 0.21) were virtually identical to those who remained free of disease (0.29, 0.50, 0.21; P = .9). There was no evidence of association between the Alu insertion polymorphism and risks of future myocardial infarction in models assuming either allelic recessive (relative risk, 1.05; 95% confidence interval, 0.8 to 1.4, P = .8) or allelic dominant (relative risk, 1.04; 95% confidence interval, 0.7 to 1.5, P = .8) modes of inheritance, nor were associations found in analyses stratified by age, family history, hypercholesterolemia, or the presence of other risk factors for premature coronary disease. Multivariate analysis had no important effects on these relationships. In this cohort of middle-aged US men, the presence of the insertion allele of the Alu-repeat polymorphism of the tissue-type plasminogen activator gene is not associated with future risks of myocardial infarction.
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PMID:Alu-repeat polymorphism in the gene coding for tissue-type plasminogen activator (t-PA) and risks of myocardial infarction among middle-aged men. 932 64

Blood vessels affect the quality of life in many ways. They provide an essential nutritive function during growth and repair of tissues but, on the other hand, can become affected by disorders or trauma, resulting in bleeding, thrombosis, arterial stenosis, and atherosclerosis. Three molecular systems, the vascular endothelial growth factor (VEGF) system, the plasminogen system, and the coagulation system, have been implicated in the formation and pathobiology of blood vessels. This review focuses on the role of these systems in these processes. Recent gene-targeting studies have identified VEGF as a potent modulator of the formation of endothelial cell-lined channels. Somewhat unanticipated, the initiator of coagulation is not only involved in the control of hemostasis but also in the maturation of a muscular wall around the endothelium. With different murine models of cardiovascular disease, a pleiotropic role of the plasminogen system was elucidated in thrombosis, in arterial neointima formation after vascular wound healing and allograft transplantation, in atherosclerosis, and in the formation of atherosclerotic aneurysms. Surprisingly, tissue-type plasminogen activator is also involved in brain damage after ischemic or neurotoxic insults. The insights from these gene-targeting studies have formed the basis for designing gene therapy strategies for restenosis and thrombosis, which have been successfully tested in these knockout models.
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PMID:Molecular analysis of blood vessel formation and disease. 937 41

The relation between LDL subfractions and fibrinolytic activity was studied in 150 men aged 53 to 63 years. Apolipoprotein B (apoB) concentration in the most dense LDL-5 (r = 0.39, p <0.001) and LDL-6 (r = 0.43, p <0.001) subfractions associated with plasminogen activator inhibitor type-1 (PAI-1) activity. Subjects in the highest LDL-6 apoB tertile had higher PAI-1 (24.7 vs. 13.1 AU/ml, p <0.001) and lower t-PA (0.26 vs. 0.54 IU/ml, p <0.001) activities than men in the lowest tertile. The difference in PAI-1 remained after adjusting for either triglycerides (p = 0.039) or insulin (p = 0.015) with cardiorespiratory fitness as an additional covariate, and history of cardiovascular disease and smoking as factors. In a regression analysis, plasma insulin and LDL-6 apoB, but not plasma triglycerides and body mass index, entered the model, and explained 30.6 and 3.9% of the variance in PAI-1 activity, respectively. The novel finding of the present study was the independent association between small, dense LDL particles and PAI-1 activity in middle-aged men.
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PMID:Small, dense LDL particle concentration correlates with plasminogen activator inhibitor type-1 (PAI-1) activity. 942 1

Adverse changes in coagulation and fibrinolytic factors are thought to contribute to the increased risk of cardiovascular disease and atherothrombosis with age. We tested the hypothesis that such age-related changes in specific coagulation and fibrinolytic factors are absent in physically active women. Resting levels of plasma fibrinogen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor-1 (PAI-1) antigen and activity, and fibrin D-dimer were measured in 24 healthy premenopausal women: 11 sedentary (aged 28+/-1 years; Pre-S) and 13 physically active (aged 30+/-1 years; Pre-PA) and in 27 healthy postmenopausal women: 14 sedentary (aged 61+/-1 years; Post-S) and 13 physically active (aged 58+/-1 years; Post-PA). Post-S had higher (P<.05) fibrinogen, t-PA antigen, PAI-1 antigen, PAI-1 activity, and fibrin D-dimer levels and lower t-PA activity than Pre-S. Post-PA demonstrated lower (P<.01) plasma fibrinogen, t-PA antigen, PAI-1 antigen, and PAI-1 activity and higher (P<.01) t-PA activity levels than Post-S. In addition, plasma fibrin D-dimer levels tended (P=.06) to be lower in Post-PA than in Post-S. Although plasma levels of fibrinogen and fibrin D-dimer in Post-PA were lower than in Post-S, they were higher (P<.05) than in Pre-PA. Importantly, however, the fibrinolytic profile of Post-PA did not differ from that of Pre-PA. The results of the present study demonstrate that the adverse age-associated differences in plasma fibrinogen concentrations and the endogenous fibrinolytic system in sedentary healthy women are either attenuated or absent in highly physically active women. The smaller or absent age-related differences in coagulation and fibrinolytic factors in women who habitually exercise may represent an important mechanism contributing to their lower age-related increase in both cardiovascular disease and atherothrombotic events. Future studies need to determine whether women who are moderately active would demonstrate the same favorable hemostatic profile.
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PMID:Physical activity status and adverse age-related differences in coagulation and fibrinolytic factors in women. 951 4

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44

Prinzmetal's variant angina, primarily a vasospastic disease, is a glaring example of the gaps in our knowledge regarding the etiology of coronary heart disease. Half of all patients with coronary heart disease do not have any of the established coronary risk factors. Prinzmetal's variant angina, syndrome X, coronary embolization, and congenital coronary anomalies, are a few examples of conditions that may not be associated with established risk factors. New risk factors that are emerging in an attempt to establish an etiology in this group of patients are homocysteine plasma fibrinogen, estrogen-deficiency lipoprotein (a), C-reactive protein, Chlamydia pneumoniae, factor VII endogenous tissue plasminogen, and endogenous plasminogen activator/inhibitor type I. The battle against cardiovascular disease continues!
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PMID:Fifty percent of patients with coronary artery disease do not have any of the conventional risk factors. 957 51

Strong evidence from large observational epidemiological studies links haemostatic variables to the future risk of myocardial infarction and stroke. Recent data provide further evidence for an early involvement of haemostatic parameters in atherosclerosis. So far, a variety of markers of a procoagulatory tendency e.g. elevated fibrinogen, coagulation factor VII, factor VIII and von Willebrand factor, platelet hyperaggregation, increased plasma levels of D-dimer, and decreased fibrinolytic capacity, e.g. characterized by increased levels of PAI-1 activity and decreased t-PA concentrations have been identified prospectively. Thus, a complex disturbed haemostatic system plays an important role in the development of atherothrombotic events in several vascular beds. This review discusses the epidemiologic evidence of the association between the haemostatic system and cardiovascular disease.
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PMID:Haemostatic risk factors for cardiovascular diseases. 959 24


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