Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three enzyme-linked immunosorbent assays for the quantitation of murine tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor 1 (PAI-1), were developed using monoclonal antibodies raised against the autologous proteins in gene-inactivated mice. Dose-response was linear for t-PA and PAI-1 between 5 and 0.1 ng/ml and for u-PA between 50 and 1 ng/ml, with intra-assay, inter-assay and inter-dilution coefficients of variation of 6 to 14%. Assay recoveries of proteins (5 to 100 ng/ml) added to plasma were 73 to 95% for t-PA and PAI-1. Linear correlations (r = 0.65, r = 0.91 and r = 0.92, for t-PA, u-PA and PAI-1 respectively) were found between antigen and activity in plasma, urine and tissue extracts. Levels of t-PA and PAI-1 antigen in murine plasma were 2.5 +/- 1.0 ng/ml (mean +/- SD, n=9) and 1.9 +/- 0.6 ng/ml (mean +/- SD, n = 8), respectively, in wild-type mice and undetectable in gene-inactivated mice. Bradykinin injection in mice provoked a 12-fold increase (p < 0.0002) of t-PA and endotoxin injection an 80-fold increase (p < 0.005) of PAI-1 levels. u-PA antigen levels in urine from wild-type mice ranged between 0.2 and 8.2 micrograms/ml (1.8 +/- 1.9 micrograms/ml, mean +/- SD, n = 17) and were undetectable in gene-inactivated mice. Thus, these assays may be useful for studies on the role of these proteins in tissue remodeling, atherosclerosis, embryogenesis, etc., in established mouse models. Gene-inactivated mice may constitute a general approach for the generation of monoclonal antibodies against the deficient translation products and for the development of specific immunoassays for murine proteins.
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PMID:Immunoassay of murine t-PA, u-PA and PAI-1 using monoclonal antibodies raised in gene-inactivated mice. 860 14

We evaluated the genotypes of the angiotensin-converting enzyme (ACE) gene in 101 subjects with and 109 subjects without a history of ischemic stroke. All were attending a metabolic ward. The two groups were compared for major risk factors for ischemic events. Genotypes were determined by polymerase chain reaction with oligonucleotide primers flanking the polymorphic region in intron 16 of the ACE gene. Deletion polymorphism of the ACE gene (DD genotype) was shown to be more common in subjects with a history of stroke than in those without (relative risk, 1.76; confidence intervals, 1.02 to 3.05). A positive family history for ischemic complications of atherosclerosis was also more common in subjects with documented events (relative risk, 1.99; confidence intervals, 1.10 to 3.59). DD genotype and a positive family history were strong independent discriminators of cerebral ischemia. Plasma levels of tissue-type plasminogen activator (TPA) and plasminogen activator inhibitor-1 help identify subjects with a history of cerebral ischemic episodes. When such fibrinolytic variables were included in the analysis, the DD genotype still strongly and independently discriminated subjects with a stroke history and significantly interacted with TPA levels > 10 ng/mL in such identification. We conclude that in subjects attending a metabolic ward, homozygosity for a deletion polymorphism of the ACE gene consistently discriminates subjects with a stroke history. Interaction with TPA improves such identification.
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PMID:Deletion polymorphism in the angiotensin-converting enzyme gene in patients with a history of ischemic stroke. 862 Mar 47

Atherosclerosis and thrombosis, two major causes of morbidity and mortality in renal transplant recipients, share the same clinical risk factors including decreased fibrinolysis and lipid disturbances. In a cross-sectional study we have determined parameters of fibrinolysis in control subjects (n = 23) and stable renal allograft recipients without cyclosporin (CsA) (n = 10) and with CsA (n = 87) in their immunosuppressive treatment. In CsA-treated patients, tissue-type plasminogen activator was moderately increased compared to patients without CsA (8.4+/-3.3 vs 5.5+/-2.8 ng/ml). The plasminogen activator inhibitor (PAI) activity in plasma was clearly increased in CsA-treated patients: 14.5+/-8.8 vs 7.2+/-3.2 in normal controls and 8.5+/-2.4 AU/ml in patients without CsA. Total cholesterol and LDL cholesterol levels were higher in CsA-treated patients (256+/-62 and 169+/-60 mg/dl) than in patients without CsA (209+/-45 and 136+/-44 mg/dl). The two groups did not differ in HDL cholesterol, triglycerides, and lipoprotein(a). Hypercholesterolaemia, obesity, and steroid-induced diabetes could be identified as risk factors for elevated plasma PAI activity in CsA-treated patients. Hypofibrinolysis induced by elevated PAI levels and increased LDL cholesterol may contribute to the increased thrombogenicity and accelerated atherosclerosis observed in cyclosporin-treated patients.
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PMID:Elevated plasminogen activator inhibitor levels in cyclosporin-treated renal allograft recipients. 867 91

Cell-surface activation of plasminogen may be important in diseases that involve cellular migration, including atherosclerosis and tumour invasion/metastasis. Cytokeratin 8 (CK 8) has been identified as a plasminogen-binding protein expressed on the external surfaces of hepatocytes and breast carcinoma cells [Hembrough, Vasudevan, Allietta, Glass and Gonias (1995) J. Cell Sci. 108, 1071-1082]. In this investigation, we demonstrate that a soluble form of CK 8 is released into the culture medium of breast cancer cell lines. The released CK 8 is in the form of variably sized polymers that bind plasminogen and promote the activation of [Glu1]plasminogen and [Lys78]plasminogen by single-chain tissue-type plasminogen activator (sct-PA). To assess the mechanism by which CK 8 promotes plasminogen activation, CK 8 was purified from rat hepatocytes and immobilized in microtitre plates. Immobilized CK 8 bound 125I-plasminogen and 125I-sct-PA in a specific and saturable manner. The KDs were 160 +/- 40 nM and 250 +/- 48 nM, respectively. Activation of plasminogen bound to immobilized CK 8 was accelerated compared with plasminogen in solution, as determined using a coupled-substrate fluorescence assay and SDS/PAGE. The ability of CK 8 to promote plasminogen activation may be important in the pericellular spaces surrounding breast cancer cells and at the cell surface.
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PMID:Cytokeratin 8 released by breast carcinoma cells in vitro binds plasminogen and tissue-type plasminogen activator and promotes plasminogen activation. 876 Mar 60

Reocclusion following thrombolysis is a major limitation of thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) because denuded vessel wall exposed to blood following thrombolysis is a favourable surface for platelet and leucocyte deposition. We have applied a chemiluminescence technique to detect superoxide radical (0(-2)) produced by leucocytes adherent to the femoral artery 24 h after photochemically induced thrombogenesis in the guinea pig in vivo and subsequent thrombolysis by rt-PA. Intravenous administration of MCLA, a specific chemiluminescence reagent for detecting O(-2), markedly increased photon emission. the photon emission was markedly potentiated by phorbol myristate acetate and was suppressed by superoxide dismutase. Reocclusion 24 h after rt-PA induced thrombolysis was observed in 10 of 16 animals. Histological observations revealed extensive polymorphonuclear leucocytes adherent to the vessel wall at the site of thrombogenesis and thrombolysis. A higher level of 0(-2) could be detected from the arteries in which thrombolysis was induced compared with those without thrombolysis. Further, the level 0(-2) detected was greater in reoccluded arteries compared with those in which reflow was established. These observations suggest that 0(-2) is produced by adherent leucocytes at the site of thrombolysis and that leucocytes are involved in reocclusion after thrombolysis.
Atherosclerosis 1996 May
PMID:A chemiluminescent detection of superoxide radical produced by adherent leucocytes to the subendothelium following thrombolysis: studies with a photochemically induced thrombosis model in the guinea pig femoral artery. 876 84

Over 200 risk factors for cardiovascular disease (CVD) have now been identified. Among these, the three most important are (1) abnormal lipids, including the fact that there are more than 15 types of cholesterol-containing lipoproteins and four different types of triglyceride-rich particles, some of which are very atherogenic, (2) high blood pressure, and (3) cigarette smoking. In addition, many other factors including diabetes, haemostatic factors such as fibrinogen, factor VII, plasminogen activator inhibitors, and new factors such as apolipoprotein E4 and homocysteine, are known to increase the risk of developing clinical CVD. A low risk for CVD requires that these various factors are present in the circulation in the correct proportions. Two simple tests for determining plasma lipid levels can be used to identify those individuals with an atherogenic lipid profile and who are, therefore, at increased risk for CVD. Firstly, the ratio of total cholesterol to high density cholesterol (HDL cholesterol) should be determined, followed by measurement of plasma triglyceride concentrations. This will allow differentiation of whether the low density lipoproteins (LDL), HDL cholesterol or triglyceride-rich particles such as the small dense beta-very low density lipoproteins (VLDL) are the major cause for concern. Once identified, those individuals with a high lipid risk profile should be treated before, rather than after, experiencing coronary heart disease (CHD).
Atherosclerosis 1996 Jul
PMID:Lipids, risk factors and ischaemic heart disease. 883 10

Some fibrinolytic parameters, whole blood and plasma serotonin were studied in normotensive and hypertensive patients with glomerulonephritis. Diminished activity of tissue plasminogen activator (tPA) and a significant prolongation of the euglobulin clot lysis time was observed in hypertensive and normotensive patients with glomerulonephritis when compared to healthy volunteers. Antigen and activity of inhibitor of tissue plasminogen activator (PAI) was found to be higher in hypertensive patients relative to control group. Whole blood serotonin was significantly lower, whereas plasma serotonin was higher in normotensive and hypertensive patients with glomerulonephritis when compared to healthy subjects. Impairment in fibrinolysis and elevated plasma serotonin levels may contribute to the increased risk of thromboembolic complications and accelerated atherosclerosis in these patients.
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PMID:[Fibrinolytic and peripheral serotonergic system in patients with glomerulonephritis]. 883 42

In this study we investigated serum Lp(a) and plasma t-PA-PAI-1 complex levels in patients with coronary heart disease (CHD). Serum total cholesterol, triglyceride, LDL and VDL cholesterol levels (p < 0.001) and HDL cholesterol levels (p < 0.01) in patients group were found to be significantly different from those in control group. The mean Lp(a) and t-PA-PAI-1 complex levels in patients with coronary heart disease were significantly higher as compared to control group (p < 0.001). This data indicate that the elevated levels of serum Lp(a) and plasma t-PA-PAI-1 complex may play an important role in the pathogenesis of coronary atherosclerosis.
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PMID:Plasma Lp(a) and t-PA-PAI-1 complex levels in coronary heart disease. 883 6

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

The syndrome of growth hormone deficiency (GHD) in adults is associated with premature atherosclerosis, increased cardiovascular mortality, abnormal lipoprotein patterns and abnormal body composition. We have previously shown that GH-deficient adults have increased concentrations of fibrinogen and plasminogen activator inhibitor (PAI-1) activity. The aim of the present investigation was to study coagulation and fibrinolysis in 17 patients with adult-onset GHD during two years of treatment with recombinant human GH (12 micrograms/kg body weight/day). The impact of the contemporary changes in metabolic variables and body composition on coagulation and fibrinolysis was studied. The patients received conventional thyroid, adrenal and gonadal hormone replacement therapy. PAI-1 activity, PAI-1 antigen and tissue plasminogen activator (t-PA) antigen levels decreased during the GH treatment period (p < 0.05). The decrease was more pronounced in patients with high pre-treatment levels of the different variables. alpha 2-antiplasmin decreased (p < 0.05), while plasminogen was unchanged during two years of GH treatment. Fibrinogen concentrations tended to decrease after two years of GH treatment (p = 0.06), while the coagulation factors VII and VIII were unchanged. von Willebrand factor demonstrated a transient decrease after 18 months of GH treatment. The coagulation inhibitor, protein C, decreased (p < 0.05), while antithrombin was unchanged. Fasting plasma insulin increased (p < 0.01), but blood glucose did not differ after two years of GH treatment. Serum high-density lipoprotein cholesterol, total cholesterol and triglycerides were unaltered. Body fat decreased during the initial GH treatment but was unaltered after two years, while lean body mass increased (p < 0.001) and the waist over hip circumference ratio tended to decrease (p = 0.06). In conclusion, PAI-1 activity, PAI-1 antigen and t-PA antigen decreased during long-term GH treatment. These changes may be a direct effect of GH itself or may be secondary to the favourable changes in body composition. It remains to be seen whether changes in these fibrinolytic variables during rhGH treatment reduces the cardiovascular risk in patients with GHD. The present results suggest that GH plays a role in the regulation of fibrinolysis.
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PMID:Long-term treatment with growth hormone decreases plasminogen activator inhibitor-1 and tissue plasminogen activator in growth hormone-deficient adults. 888 81


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