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)

The aim of this study was to examine whether there was a relationship between ultrasound-assessed morphology of the femoral artery wall and hemostatic factors, and whether these factors were associated with intermittent claudication. One hundred and thirty men at high cardiovascular risk and 51 men at low risk were examined. The subjects (high- and low-risk) with moderate/large plaque (n = 96) had higher fibrinogen, thrombin/antithrombin complex and von Willebrand factor, compared to subjects with small/no plaque. The maximum intima-media thickness of the femoral artery was significantly associated with fibrinogen. These associations were independent of current smoking habits. Clinical atherosclerosis was associated with fibrinogen, von Willebrand factor, thrombin/antithrombin complex, plasminogen activator inhibitor activity, mean and maximum intima-media thickness and plaque status of the femoral artery. In conclusion, fibrinogen, von Willebrand factor and thrombin/antithrombin complex were related to plaque occurrence in the femoral artery. Clinical atherosclerosis was associated with fibrinogen, von Willebrand factor, thrombin/antithrombin complex and plasminogen activator inhibitor activity.
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PMID:Femoral artery wall morphology, hemostatic factors and intermittent claudication: ultrasound study in men at high and low risk for atherosclerotic disease. 869 78

Vascular endothelium is strategically located at the interface between tissue and blood. It is pivotal for protecting against vascular injury and maintaining blood fluidity. Normal endothelium releases prostacyclin and nitric oxide, potent inhibitors of platelet and monocyte activation and vasodilators. Their syntheses are governed by isoforms of enzymes. Normal endothelial surface expresses ecto-adenosine diphosphatase, which degrades adenosine diphosphate and inhibits platelet aggregation; thrombomodulin, which serves as a binding site for thrombin to activate protein C; and heparin-like molecules, which serve as a cofactor for antithrombin III. Normal endothelium secretes tissue plasminogen activator, which activates the fibrinolysis system. Endothelium produces and secretes von Willebrand factor, which mediates platelet adhesion and shear-stress-induced aggregation. Injury to endothelium is accompanied by loss of protective molecules and expression of adhesive molecules, procoagulant activities, and mitogenic factors, leading to development of thrombosis, smooth muscle cell migration, and proliferation and atherosclerosis.
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PMID:Role of endothelium in thrombosis and hemostasis. 871 85

To determine relationships between haemostatic and rheological factors and severity of peripheral atherosclerosis and differences by site, an angiographic cross-sectional survey was carried out on 192 men and women with intermittent claudication or rest pain. 34 patients were classified as having aorto-iliac disease, 85 femoro-popliteal disease and 73 dual-site disease. Mean levels of haemostatic or rheological factors did not differ significantly between the three site groups. In all 192 patients, disease severity in the femoro-popliteal segments was correlated with plasma nephelometric fibrinogen (r = 0.20, p < or = 0.01), von Willebrand factor (r = 0.14, p < or = 0.05) and fibrin D-dimer (r = 0.22, p < or = 0.001). On multiple regression analyses, fibrinogen was independently associated with disease severity in the femoro-popliteal segments (p < or = 0.05), but not in the aorto-iliac segments. Adjustment for packyears or serum thiocyanate had little effect on the association of fibrinogen with severity of disease. An inverse relationship between plasminogen activator inhibitor and disease severity in the femoro-popliteal segments was found only in men (r = 0.24, p < or = 0.01). We conclude that elevated fibrinogen and disturbed fibrinolytic activity may be related to the extent of disease within the femoro-popliteal arteries, more so than in the aorto-iliac arteries.
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PMID:Smoking, haemostatic factors and the severity of aorto-iliac and femoro-popliteal disease. 871 74

The endothelial L-arginine:nitric oxide (NO) system is fundamental to vascular function. It is becoming evident that this system is compromised in aorto-coronary vein grafts, although it is not clear how it is affected. It was postulated that the development of intimal lesions in vein grafts may be associated with reduced expression or loss of endothelial NO synthase (eNOS). The immunocytochemical localization and quantitative expression of eNOS were therefore investigated in normal human saphenous veins (n = 6) and explanted vein grafts (n = 6). The vein grafts demonstrated marked morphological changes evident as fibro-intimal hyperplasia (FIH) and focal sites of atherosclerosis, often occurring along the same length of graft. Staining for eNOS was abundantly evident in the endothelium of normal veins but revealed a differential reduction in staining intensity in vein grafts. Staining intensity measurements revealed a significant reduction (P < 0.001) in the amount of eNOS present in areas of atherosclerosis as compared with normal veins and areas of vein graft with FIH changes alone. This reduction in the relative quantity of antigen was specific to eNOS, since the endothelial markers von Willebrand factor (vWf) and CD31 showed no such variations. These data support the view that vascular activity of NO is impaired in atherosclerosis and indicate that reduced expression of eNOS, and therefore by inference lower NO production, may make an important contribution to this phenomenon.
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PMID:Explanted vein grafts with an intact endothelium demonstrate reduced focal expression of endothelial nitric oxide synthase specific to atherosclerotic sites. 875 13

Mast cells have been assigned a role in neovascularization. Therefore, we examined the deep regions of human coronary atheromas, the areas known to be prone to neovascularization, for the presence of mast cells. Specimens of atherosclerotic human coronary intima from 37 autopsy cases with ages of 24-84 years were stained with elastica-van Gieson to detect atheroma formation and with monoclonal antibody against von Willebrand factor to detect neovascularization. Mast cells were detected by staining the atheromas with monoclonal antibodies against the two major proteases of mast cells, tryptase and chymase. Of the 24 coronary atheromas found, 13 contained mast cells in the deep regions. All these 13 deep regions also displayed neovascularization, and the number of microvessels and the number of mast cells around the microvessels correlated strongly with the size of the atheroma. On the other hand, of the 11 deep regions lacking mast cells, only one displayed neovascularization. In the neovascularized areas of the coronary atheromas, the mast cells were in close proximity to the microvessels. All the mast cells contained tryptase, and some of them chymase, both known for their angiogenic and matrix-degrading potential. In light microscopic studies, degranulated mast cells were observed indicating activation of these cells, with release of tryptase and chymase. The selective localization of activated mast cells containing angiogenic factors around newly formed microvessels in human coronary atheromas suggests that mast cells play a role in the neovascularization of these lesions. Moreover, mast cells may also, by virtue of their neutral proteases, injure the microvessels, and thereby produce intraplaque hemorrhages and, ultimately, unstable lesions.
Atherosclerosis 1996 Jun
PMID:Mast cells accompany microvessels in human coronary atheromas: implications for intimal neovascularization and hemorrhage. 878 43

Uraemic patients suffer from haemorrhagic disorders and accelerated atherosclerosis. To evaluate the possible role of the vessel wall in these haemostatic alterations associated with uraemia, we investigated the effect of a uraemic milieu on human endothelial cell (EC) cultures and the reactivity of the extracellular matrices (ECM) generated by these cells towards platelets. EC cultures were exposed to a pool of sera (20% in the culture medium) obtained either from uraemic patients or from normal donors, and the following parameters were evaluated: (1) EC viability (trypan blue exclusion test); (2) von Willebrand factor (vWF) levels in supernatants and associated with ECM; (3) the reactivity of EC and EC-derived ECM towards platelets, measured 'ex vivo' under flow conditions (5 min, wall shear rate 800 s-1); and (4) ultrastructure of the ECM. The viability of EC cultured in the presence of uraemic sera was similar to controls. Platelet interaction with ECM generated by EC exposed to uraemic sera was significantly reduced (P < 0.05). This decrease was mainly related to a reduction in platelet adhesion (9.8 +/- 1.9% vs 16.7 +/- 1.8% in controls, P < 0.02). VWF levels in supernatants and associated with ECM were similar to controls. Ultrastructural analysis of the ECM generated by EC exposed to uraemic sera revealed a deficient matrix. An increased removal of EC was observed in experiments in which EC cultured in the presence of uraemic sera were perfused with citrated blood. These results indicate that a uraemic milieu induces quantitative and qualitative changes in the vascular subendothelium, characterized by a less intrincate network of fibrils, as well as a decreased attachment of EC and reduced thrombogenicity to the ECM. These changes may represent another mechanism which contributes to the haemostatic dysfunction observed in uraemic patients.
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PMID:Uraemic medium causes endothelial cell dysfunction characterized by an alteration of the properties of its subendothelial matrix. 880 11

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

The baseline examination (1987-1989) for the Atherosclerosis Risk in Communities (ARIC) Study was conducted in 15,792 free-living residents aged 45-64 years in four geographically dispersed US communities. A questionnaire on symptoms of transient ischemic attack (TIA) and stroke was evaluated by computer algorithm for 12,205 of these participants. Data were also collected on lipoprotein levels, hemostasis, hematology, anthropometry, blood pressure, medical history, lifestyle, socioeconomic status, and medication use. Noninvasive high resolution B-mode ultrasonographic imaging was used to determine carotid arterial intimal-medial wall thickness (IMT). The cross-sectional relation between the prevalence of TIA/stroke symptoms and putative risk factors was assessed by logistic regression, controlling for age and community. Odds ratios for TIA/stroke symptoms were significantly elevated (p < or = 0.01) for diabetes mellitus, current smoking, hypertension, lower levels of education, income, and work activity, and higher levels of lipoprotein(a), IMT, hemostasis factor VIII, and von Willebrand factor. However, the relations with education and carotid IMT were not present for black Americans. In whites, the relations of TIA/stroke symptoms to IMT were nonlinear. Only at extreme levels of IMT were symptoms substantially more frequent: For example, men with an IMT greater than 1.17 mm or women with an IMT greater than 0.85 mm had approximately twice the odds of having positive TIA/stroke symptoms as those with lower IMTs. The authors plan in future analyses to address the issue prospectively, as well as to examine the relation with magnetic resonance imaging-defined outcomes and clinically defined incident stroke.
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PMID:Association of transient ischemic attack/stroke symptoms assessed by standardized questionnaire and algorithm with cerebrovascular risk factors and carotid artery wall thickness. The ARIC Study, 1987-1989. 889 Jun 64

There is some clinical evidence that cyclosporine A (CyA) is associated with thrombotic complications of bone marrow and renal transplantation. We investigated plasma concentrations of lipoprotein(a) [Lp(a)], a potentially atherothrombotic lipoprotein, and hemostatic and vascular status in ten patients with aplastic anemia receiving CyA, eleven patients not taking it, and 38 age-matched healthy controls. Patients receiving CyA had significantly higher concentrations of plasma fibrinogen (P < 0.05), prothrombin fragment 1 + 2 (F1 + 2; P < 0.05), plasminogen activator inhibitor-1 (PAI-1; P < 0.05), and von Willebrand factor antigen (P < 0.05) than did patients not taking CyA. Plasma concentrations of Lp(a) were higher in CyA-treated patients than those not receiving it (P < 0.05) or healthy controls (P < 0.05). The difference in the Lp(a) concentration between controls and patients who did not receive CyA-treatment was not significant. Our results suggest that hypercoagulability is likely to occur during CyA therapy. Further, the presence of high concentrations of Lp(a) may accelerate the process of atherosclerosis and increase thrombotic events in patients receiving long-term CyA.
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PMID:Hypercoagulability and high lipoprotein(a) levels in patients with aplastic anemia receiving cyclosporine. 889 50


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