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)

A link between cytomegalovirus (CMV) infection and atherosclerosis has been suggested by experimental, clinical, and epidemiologic studies. We investigated the association between CMV antibody titers in serum collected in 1974 in 300 adult residents in Washington County, Md, and hemostatic parameters in plasma collected in 1987 through 1989, when these individuals participated in the baseline examination of the Atherosclerosis Risk in Communities Study. The cross-sectional association of CMV serum antibodies and hemostatic parameters was also explored in another set of Atherosclerosis Risk in Communities cases and controls. In the longitudinal analyses, CMV titers in 1974 were directly associated with 1987 through 1989 plasma levels of von Willebrand factor, factor VIII, and protein C and negatively associated with activated partial thromboplastin time. In the cross-sectional analyses, CMV titers were directly related to antithrombin III and fibrinogen levels. When the association between CMV antibodies and atherosclerosis was examined in stratified analyses, a significant association was restricted to individuals with high levels of lipoprotein(a) and fibrinogen. These results are compatible with previous evidence suggesting that CMV virus might have procoagulant properties. The possible synergism of CMV infection and resulting hypercoagulability with reduced fibrinolysis due to increased lipoprotein(a) levels deserves further investigation.
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PMID:Cytomegalovirus infection, lipoprotein(a), and hypercoagulability: an atherogenic link? 932 77

We have investigated the effects of oxidized low density lipoproteins (oxidized LDL) on the expression of TM by THP-1 monocytic cells. TM antigen levels and its cofactor activity for thrombin-dependent protein C activation were increased by oxidized LDL and accompanied by an increase in TM mRNA levels. Incubation of THP-1 cells with 300 microg/ml oxidized LDL for 24 h resulted in an 80% increase of cellular TM antigen levels. Native LDL and acetylated LDL did not affect the TM expression by these cells. The resultant aqueous phase after extraction of oxidized LDL by chloroform/methanol increased the TM antigen levels as well as oxidized LDL. Phorbol 12-myristate 13-acetate (PMA) also increased the TM antigen level 2.1 times the control and was accompanied by the adhesion of cells to plastic dishes and increasing macrophage cell surface antigen CD14 levels. In contrast, oxidized LDL did not induce differentiation to the macrophage. The present results indicate that oxidized LDL increases cellular TM antigen without cellular differentiation and that up-regulation of TM by oxidized LDL in monocytes may have some implication in atherosclerosis.
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PMID:Effect of oxidized low density lipoprotein on thrombomodulin expression by THP-1 cells. 936 89

Older oral contraceptive (OC) formulations containing high doses of potent synthetic estrogens and progestins are associated with increased risk of thrombosis. To examine the effects of current low-dose OC and hormone replacement therapy (HRT) regimens on arterial thrombosis, premenopausal and surgically postmenopausal cynomolgus monkeys were divided into four treatment groups. Premenopausal monkeys were given either no OCs or ethinyl estradiol and levonorgestrel as an OC at a dose equivalent to that currently given to women. Postmenopausal monkeys were given either no HRT or conjugated equine estrogens and medroxyprogesterone as an HRT at a dose equivalent to that currently given to women. The monkeys were fed an atherogenic diet containing these treatments for 27 to 30 months. At the end of this time, arterial thrombosis was evaluated with a standardized stenosis/injury procedure in the left carotid artery. Blood flow velocity was monitored for cyclic or permanent occlusive thrombosis. The current OC and HRT regimens did not increase the susceptibility of the artery wall to develop an occlusive thrombus following injury and stenosis. In fact, there was a reduction in the incidence of thrombosis in the OC animals compared with untreated controls. Increased amounts of atherosclerosis were associated with an increased incidence of occlusive arterial thrombosis. Several selected coagulation parameters [von Willebrand factor, protein C, lipoprotein(a), and platelet aggregation] did not appear to be associated with either the amount of atherosclerosis or incidence of arterial thrombosis.
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PMID:Oral contraceptives and hormone replacement therapy do not increase the incidence of arterial thrombosis in a nonhuman primate model. 944 61

Measures of fibrinolytic and thrombotic function have been examined in 55 subjects with recently identified coronary heart disease, and age and sex matched control subjects. Measurements were particularly directed at factors and processes which could be affected by changes in endothelial function and included the euglobulin lysis time as well as plasma levels of von Willebrand factor (vWF). Plasma levels of protein S and protein C were also measured. Measurements were made before and after a period of 10-min veno-occlusion combined with rhythmic hand exercise. In addition anthropometric, haemodynamic and biochemical measurements (plasma lipids and apolipoproteins, glucose and insulin) were obtained and correlated with the haematological parameters. Protein S and vWF levels were significantly higher, both before and after veno-occlusive exercise, in subjects with CHD than in the asymptomatic controls. Euglobulin lysis times were not significantly different but only shortened on veno-occlusive exercise in those without CHD. Protein S levels were significantly correlated with systolic blood pressure, plasma total cholesterol, plasma triglyceride, plasma phospholipid, plasma fasting glucose and both apolipoprotein A1 and B levels. vWF levels were not significantly related to any of the other variables. Subjects whose pre-exercise euglobulin lysis times exceeded 6 h had significantly higher BMI, plasma total cholesterol, triglyceride, phospholipid, insulin, glucose and apoB concentrations and lower HDL cholesterol than those with lysis in less than 6 h. The findings from this study are consistent with a role for endothelial dysfunction in the production of atherosclerotic vascular disease and may indicate additional, non-haemodynamic, mechanisms for such an association. In addition, the relationship between elevated levels of protein S and CHD does not appear to depend on the demonstrated associations between protein S and a number of other cardiovascular risk factors.
Atherosclerosis 1998 Sep
PMID:Relationships between protein C, protein S, von Willebrand factor and euglobulin lysis time and cardiovascular risk factors in subjects with and without coronary heart disease. 973 15

BACKGROUND: Thrombophilia may be associated with premature atherosclerosis, an increased susceptibility to primary arterial thrombosis and an increased failure rate for peripheral vascular or endovascular interventions. The aim of this study was to determine the prevalence of thrombophilia in patients with intermittent claudication (IC). METHODS: This was a prospective study of 116 consecutive new patients (70 men; median age 65 (range 43-84) years) referred to this regional vascular surgery unit with IC. Patients on warfarin, or who had previously undergone lower limb reconstruction and/or angioplasty, were excluded. RESULTS: Thrombophilia was demonstrated in 24 patients (21 per cent). The commonest abnormality (15 patients, 13 per cent) was a raised level of anticardiolipin antibody (ACLA) (11 immunoglobulin (Ig) M, four IgG). Other abnormalities comprised: lupus anticoagulant (one), protein C deficiency (two), protein S deficiency (two), activated protein C resistance (one) and factor V Leiden heterozygosity (three). All abnormalities were confirmed on repeat testing. No patient had a history of venous thrombosis. There was no statistically significant relationship between ACLA status and age, sex, ankle : brachial pressure index, previous myocardial infarction or stroke, previous carotid endarterectomy or coronary artery surgery, serum cholesterol, current use of antiplatelet agents or current smoking status. CONCLUSION: Almost one-quarter of new patients referred to this regional vascular unit with IC have thrombophilia; over half of those affected have a raised ACLA level compatible with the antiphospholipid syndrome. At present, the clinical significance and management implications of these abnormalities remain unknown.
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PMID:Vascular surgical society of great britain and ireland: prevalence and significance of thrombophilia in patients with intermittent claudication 1036 36

To examine the effects of atherosclerosis on the protein C anticoagulant pathway in vivo, we measured anticoagulant responses to intravenous administration of human alpha-thrombin or activated protein C (APC) in cynomolgus monkeys. Two groups of monkeys were fed either a control diet (n=18) or an atherogenic diet (n=12) that produces both hypercholesterolemia and moderate hyperhomocyst(e)inemia. A third group (n=8) was fed an atherogenic diet for 15 months, and then fed the atherogenic diet supplemented with B vitamins for 6 months to correct the hyperhomocyst(e)inemia. The plasma homocyst(e)ine level was higher in monkeys fed the atherogenic diet (9.6+/-1.0 micromol/L) than in monkeys fed the control diet (3.7+/-0.2 micromol/L) or the atherogenic diet with B vitamins (3.6+/-0.2 micromol/L) (P<0.001). Infusion of thrombin produced a much greater prolongation of the activated partial thromboplastin time in monkeys fed the control diet (52+/-10 seconds) than in monkeys fed the atherogenic diet either with (24+/-4 seconds) or without (27+/-5 seconds) supplemental B vitamins (P<0.02). Thrombin-dependent generation of circulating APC was higher in control (294+/-17 U/mL) than in atherosclerotic (240+/-14 U/mL) monkeys (P<0.05), although levels of fibrinogen, plasminogen, D-dimer, and thrombin-antithrombin complexes were similar in each group. Injection of human APC produced a similar prolongation of the activated partial thromboplastin time in control (31+/-3 seconds) and atherosclerotic (29+/-2 seconds) monkeys. These findings provide evidence for impaired anticoagulation, due partly to decreased formation of APC, in atherosclerosis. The blunted anticoagulant response to thrombin in hypercholesterolemic monkeys was not corrected by supplementation with B vitamins.
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PMID:Impaired anticoagulant response to infusion of thrombin in atherosclerotic monkeys associated with acquired defects in the protein C system. 1039 93

Vascular brain diseases are ranked the third as the cause of morbidity and mortality, in spite of the progress in diagnostic, therapeutic and preventive procedures. In the majority of cases of vascular brain diseases, it is ischemic brain disease, which is the final and the most severe stage of cerebral arteries atherosclerosis. Etiopathogenesis of atherosclerosis is not closer defined yet, but oxidative hypothesis is distinguished among the numerous theories. Within this theory, main place is attached to oxidative modification of LDL and Lp(a), together with numerous physiopathologic facts with the central role of reactive oxidative matters, where endothelial dysfunction is the main disorder responsible for the onset of numerous impairments, such as changes in coagulation-anticoagulation system. Considering these facts, it was established the hypothesis that in patients with IBD existed changes in hemostatic system, which were in positive correlation with the degree of cerebral atherosclerosis. The study comprised 36 patients with acute IBD and 28 patients with atherosclerotic encephalopathy. Control group was comprised of 30 patients with non-vascular diseases of similar characteristics. We investigated the correlation of the changes in hemostatic system (platelet aggregation, anti-thrombin III, D-dimer, protein C, factor VII, factor VIII, PAI-1) compared to the degree of cerebral atherosclerosis (ultrasonographically) and compared to the observed groups of patients. On the basis of all, the results of this study revealed significant increase of procoagulant factors concentration in patients with IBD, and similar changes were observed in patients with atherosclerotic encephalopathy, but less pronounced. All these changes in the total sample of patients, and particularly in patients with the pronounced cerebral atherosclerosis, are of primary and chronic character.
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PMID:The influence of the degree of cerebral atherosclerosis on the changes in hemostatic system in patients with ischemic brain disease and atherosclerotic encephalopathy. 1064 49

Lipoprotein and hemostatic profiles including coagulation inhibitors were determined in 136 patients with acute ischemic stroke. Based on clinical examination, cerebral computed tomography, Doppler ultrasonography of precerebral arteries and transthoracic echocardiography, the strokes were classified as cardioembolic (n = 38), non-cardioembolic (n = 92), and mixed cardioembolic/hypertensive (n = 6). Patients with cardioembolic stroke were older than patients with non-cardioembolic stroke. Lipoprotein(a) was higher in the cardioembolic than in the non-cardioembolic group. Lipoprotein(a) was not significantly correlated to the other lipid levels and may represent an independent lipid risk factor. The non-cardioembolic group had higher levels of total cholesterol, triglycerides, total cholesterol/high-density lipoprotein cholesterol ratio, low-density lipoprotein cholesterol, apolipoprotein A1, and apolipoprotein B. The cardioembolic group had higher concentrations of fibrinogen and D-dimer, and lower levels of antithrombin, protein C, protein S and heparin cofactor 2 than the non-cardioembolic group. The differences in the hemostatic profile are consistent with thrombosis due to activated coagulation being more involved in the pathogenesis of cardioembolic than of non-cardioembolic stroke. Lipoprotein(a) seems to be more associated with coagulation markers of thrombosis than with atherosclerosis, whereas the other lipids mainly seem to be risk factors for atherosclerosis.
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PMID:Lipoprotein(a), other lipoproteins and hemostatic profiles in patients with ischemic stroke: the relation to cardiogenic embolism. 1068 49

The vascular endothelium influences not only the three classically interacting components of hemostasis: the vessel, the blood platelets and the clotting and fibrinolytic systems of plasma, but also the natural sequelae: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, best defined as an anti- and a prothrombotic state. Under physiological conditions endothelium mediates vascular dilatation (formation of NO, PGI2, adenosine, hyperpolarizing factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI2, removal of ADP), blocks thrombin formation (tissue factor pathway inhibitor, activation of protein C via thrombomodulin, activation of antithrombin III) and mitigates fibrin deposition (t- and scuplasminogen activator production). Adhesion and transmigration of inflammatory leukocytes are attenuated, e.g. by NO and IL-10, and oxygen radicals are efficiently scavenged (urate, NO, glutathione, SOD). When the endothelium is physically disrupted or functionally perturbed by postischemic reperfusion, acute and chronic inflammation, atherosclerosis, diabetes and chronic arterial hypertension, then completely opposing actions pertain. This prothrombotic, proinflammatory state is characterised by vaso-constriction, platelet and leukocyte activation and adhesion (externalization, expression and upregulation of von Willebrand factor, platelet activating factor, P-selectin, ICAM-1, IL-8, MCP-1, TNF alpha, etc.), promotion of thrombin formation, coagulation and fibrin deposition at the vascular wall (expression of tissue factor, PAI-1, phosphatidyl serine, etc.) and, in platelet-leukocyte coaggregates, additional inflammatory interactions via attachment of platelet CD40-ligand to endothelial, monocyte and B-cell CD40. Since thrombin formation and inflammatory stimulation set the stage for later tissue repair, complete abolition of such endothelial responses cannot be the goal of clinical interventions aimed at limiting procoagulatory, prothrombotic actions of a dysfunctional vascular endothelium.
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PMID:Endothelial function and hemostasis. 1079 71

The influence of thyroid failure on haemostasis is controversial, both hypocoagulable and hypercoagulable states have been reported. Since both subclinical and overt hypothyroidism have been associated with atherosclerosis, a hypercoagulable state in addition might represent a risk factor for thromboembolic disease. We investigated various haemostatic variables in 42 women with subclinical hypothyroidism and compared them to 66 euthyroid controls. Prothrombin time, activated partial thromboplastin time, fibrinogen, factor VII activity (FVII:C), factor VII antigen (FVII:Ag), factor VIII activity, von Willebrand factor (vWF), antithrombin III, heparin cofactor II, protein C, protein S, plasminogen, antiplasmin, plasminogen activator inhibitor and tissue plasminogen activator, as well as common lipid variables, were measured. Factor VII:C (P < 0.02) and the ratio FVII:C/FVII:Ag (P < 0.01) were significantly increased in subclinical hypothyroid patients compared to the control group. Both parameters remained higher in hypothyroid patients after exclusion of 18 women on oestrogen replacement therapy. No differences were found between the groups with respect to vWF or the other haemostatic and lipid variables tested. Patients with subclinical hypothyroidism had significantly higher levels of FVII:C. The greater increase in FVII:C compared to that of FVII:Ag, as shown by the increase in their ratio, might reflect the presence of activated FVIIa. This might mean a hypercoagulable state, which could contribute to the increased prevalence of coronary heart disease reported in such patients. A hypercoagulable state might be another argument in favour of thyroxine replacement treatment in subclinical hypothyroidism, especially in patients with additional risk factors for vascular disease.
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PMID:Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease. 1116 51


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