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)

We investigated heparin cofactor II (HC II) levels and their relationship to other haemostatic factors in the elderly in comparison with antithrombin III (AT III). We measured plasma HC II activity levels in 166 subjects aged from 61 to 99 years using a chromogenic method. HC II levels (94.4 +/- 18.5%) in the healthy elderly subjects were significantly (p less than 0.001) lower than in 40 healthy adult controls under 60 years of age (mean age: 51.5 years; 111.6 +/- 21.2%). HC II levels in the elderly subjects decreased further with age (r = 0.308, p less than 0.001) and the extent of the decrease was more marked than that for AT III (r = 0.179, p less than 0.05). There was no significant sex difference in HC II levels in the elderly. HC II levels correlated significantly with AT III levels and with acute phase reactants including sialic acid, fibrinogen, and PAI-1. HC II levels also correlated with factor VII, plasminogen, alpha 2-plasmin inhibitor, serum lipid, pseudocholinesterase, and albumin levels. These correlations were also found for AT III except active PAI-1 and tPA-PAI-1 complexes, but the correlations with acute phase reactants were stronger for HC II than AT III. We divided 154 elderly subjects into 4 groups by their pseudocholinesterase and albumin levels to estimate the effect of nutritional status on antithrombin activity in the elderly. HC II levels were normal in the elderly subjects with a good nutritional state (103 +/- 18%), but were significantly decreased in those with malnutrition (85 +/- 15%, p less than 0.001). AT III levels also showed the same tendency. These results indicate a decrease in the reserve capacity to inhibit thrombin generation at sites of atherosclerosis in response to trigger events. The deficiency of two major antithrombin factors in the elderly may indicate a tendency to thrombosis, especially in individuals with malnutrition. When considering the clinical significance of HC II, several other parameters, including age, nutritional status, hepatic synthetic ability, and the presence or absence of acute phase reaction should also be assessed.
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PMID:Heparin cofactor II deficiency in the elderly: comparison with antithrombin III. 138 49

Patients suffering from atherosclerosis may have a hypercoagulable state which is further aggravated by surgery. Thrombin, a central enzyme in the coagulation process, cleaves fibrinogen to fibrin. Therefore, inhibition of thrombin is an important anticoagulant mechanism. This is accomplished by heparin in concert with antithrombin III (AT), but vessel wall glycosaminoglycans may act as substitutes for heparin and catalyse thrombin inhibition. The present study examines whether administration of AT or heparin is effective as an anticoagulant during infrainguinal bypass surgery. Preoperatively and during surgery the patients had elevated levels of fibrinogen, fibrinopeptide A (FPA) and thrombin-antithrombin (T-AT) complexes. There were higher levels of FPA in the venous outflow from the ischemic leg than in the arterial inflow. Taken together these measurements indicate ongoing coagulation in the operated leg. Administration of heparin decreased FPA levels and prevented intraoperative graft thrombosis, whereas in patients receiving AT, T-AT levels increased but FPA levels were unchanged. In the latter group, intraoperative graft thrombosis occurred in a high proportion. Based on additional case histories in these patients with hypercoagulability, it is suggested that fibrinogen is a risk factor for thromboembolic complications and that a combination of low dose of heparin and AT might be an effective regimen to prevent intraoperative thrombosis with a low risk of haemorrhage.
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PMID:Peroperative anticoagulation with antithrombin or heparin in infrainguinal bypass surgery. 145 16

Atherosclerosis is associated with an accumulation of proteoglycans. Proteoglycans and/or glycosaminoglycans, in particular heparan sulfate, produced by endothelial cells are thought to play important roles in diverse vascular functions. Of particular note is that they possess anticoagulant functions, i.e., heparin-like antithrombin cofactor activity. Incubation of antithrombin III with endothelial cell cultures resulted in a specific, saturable binding of this protease inhibitor presumably to the endothelial cell surface. In addition, thrombin inactivation by antithrombin III was accelerated on the endothelial surface, providing strong evidence that heparan sulfate on the surface of endothelial cells exerts a heparin-like activity. beta-D-xyloside or cytokine treatments altered the synthesis of heparan sulfate on the endothelial cell surface, resulting in decreased anti-thrombin III binding and diminished heparin-like anticoagulant activity of endothelial cells. The modulation of endothelial heparin-like compounds by these pharmacologic or physiologic agents may have pathophysiologic implications in thrombosis as well as atherogenesis.
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PMID:Anticoagulant heparin-like glycosaminoglycans on endothelial cell surface. 174 77

Forty-nine regions in 21 proteins were identified as potential heparin-binding sites based on the sequence organizations of their basic and nonbasic residues. Twelve known heparin-binding sequences in vitronectin, apolipoproteins E and B-100, and platelet factor 4 were used to formulate two search strings for identifying potential heparin-binding regions in other proteins. Consensus sequences for glycosaminoglycan recognition were determined as [-X-B-B-X-B-X-] and [-X-B-B-B-X-X-B-X-] where B is the probability of a basic residue and X is a hydropathic residue. Predictions were then made as to the heparin-binding domains in endothelial cell growth factor, purpurin, and antithrombin-III. Many of the natural sequences conforming to these consensus motifs show prominent amphipathic periodicities having both alpha-helical and beta-strand conformations as determined by predictive algorithms and circular dichroism studies. The heparin-binding domain of vitronectin was modeled and formed a hydrophilic pocket that wrapped around and folded over a heparin octasaccharide, yielding a complementary structure. We suggest that these consensus sequence elements form potential nucleation sites for the recognition of polyanions in proteins and may provide a useful guide in identifying heparin-binding regions in other proteins. The possible relevance of protein-glycosaminoglycans interactions in atherosclerosis is discussed.
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PMID:Molecular modeling of protein-glycosaminoglycan interactions. 246 27

In order to carry out a multicenter study aimed at understanding the association of hemostatic factors with atherosclerotic vascular disorders for the Atherosclerosis Risk In Communities (ARIC) Study, we compared a blood collection and processing system developed in our laboratory with the state-of-the-art-procedures. The salient features of our system included the use of a new phlebotomy set for venipuncture, the use of Millipore filters for removing platelet residues in the plasma and the use of a mixture of anticoagulants and antiplatelet agents for inhibiting the in vitro activation of platelets, coagulation and fibrinolytic system. The results derived from systematic evaluations indicate that this newly developed system yields the lowest values of plasma beta TG, PF 4 and FPA when compared with the reported values. The technique also gave reliable values of representative hemostatic measurements such as fibrinogen, factor VII, factor VIII, von Willebrand factor, antithrombin-III, protein C, tissue-type plasminogen activator, and serum thromboxane B2. Further experiments revealed that the samples withstood temporary storage at -70 degrees C and overnight "shipping" manipulations without significant changes in the hemostatic values. We conclude that the described blood collection and processing system may be a valuable asset for conducting multicenter cooperative clinical trials and epidemiologic studies involving blood collection by multiple field centers or clinics.
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PMID:ARIC hemostasis study--I. Development of a blood collection and processing system suitable for multicenter hemostatic studies. 252 84

A polyclonal antibody against human lipoprotein lipase (LPL) was prepared. LPL from post-heparin plasma was first purified by heparin Sepharose 4B affinity chromatography. Protein impurities co-eluted with LPL were then eliminated by electrophoresis in the presence of ampholytes. Antithrombin III was identified in this fraction of protein impurities by immunodiffusion against a human antithrombin antiserum, while no antithrombin III could be detected in the purified LPL fraction. Immunodiffusion revealed a single line of precipitation between this antibody and human post-heparin plasma LPL. When pre-incubated with a constant activity of highly purified post-heparin plasma LPL (2.7 mU/75 microliters), an equal volume of the anti-LPL antiserum, either pure or diluted to 1/32 caused complete inhibition of the enzyme activity. Half maximal inhibition was observed at a dilution of approximately 1/200. By using a secondary antibody, it was shown that antiserum inhibited LPL activity by means of its immunoglobulins. This antibody was able to inhibit LPL from human adipose tissue, indicating that human LPL released from endothelial cell membranes has common antigenic determinants with adipose tissue LPL.
Atherosclerosis 1987 Apr
PMID:Antibody against human lipoprotein lipase. 360 17

Coagulation factor VIII, von Willebrand factor, antithrombin, fibrinogen, plasminogen activator capacity, and inhibitors of fibrinolysis, including a recently discovered fast inhibitor of tissue plasminogen activator, were measured three to six months after myocardial infarction in 116 male and 32 female patients aged less than 45 and in 136 age and sex matched random controls. Plasma concentrations of fibrinogen and the fast inhibitor of tissue plasminogen activator were raised in male patients (with or without correction for orosomucoid levels, blood group distribution, tobacco and alcohol consumption, and weight/height index) and plasminogen activator capacity was reduced. In female patients the concentrations of factor VIII, von Willebrand factor, the fast inhibitor of tissue plasminogen activator, alpha 2-antiplasmin, and C1 inhibitor were significantly increased. The increase in factor VIII concentrations depended strongly on a persisting inflammatory response. Multivariate analysis indicated that a combination of fibrinogen and tissue plasminogen activator inhibitor concentrations gave the best independent discrimination between male patients and controls. For female patients the best combination was von Willebrand factor and tissue plasminogen activator inhibitor. Male patients with multiple vessel atheromatosis at coronary angiography had higher fibrinogen concentrations than those with atheromatosis of a single vessel. Atheromatosis was defined as sharp-edged, plaque-like, or irregular indentations, often multiple, into the vessel lumen without features suggesting fibromuscular hyperplasia.
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PMID:Haemostatic function in myocardial infarction. 394 83

A sample of in all 119 young adults below the age of 55, with ischemic cerebrovascular disease (TIA and minor stroke), was investigated later than three months after acute disease. Factor VIII biological activity and antithrombin antigen were significantly (p less than 0.001) increased as compared to 80 healthy controls. In combination, these two variables correctly classified 85 percent of patients and controls at a stepwise discriminant analysis. Factor VIII related antigen was increased (p less than 0.02) in patients with atherosclerotic signs at cerebral angiography and in postmenopausal female patients (p less than 0.001). It is suggested that high levels of factor VIII might predispose for thrombosis/atherosclerosis. Antithrombin biological activity was normal in spite of high antithrombin antigen levels, possibly indicating a relative insufficiency in the antithrombin defense line. It is concluded that young stroke patients provide good opportunities to look for early operating factors and predictors in human atherosclerosis and arterial thromboembolism.
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PMID:A study of hemostasis in ischemic cerebrovascular disease. I. Abnormalities in factor VIII and antithrombin. 681 Apr 96

A study is reported which tries to identify those members of the general population who may be at increased risk of vascular disease. It is probable that patients who have had previous thrombotic episodes are inherently more at risk of further episodes and that a thrombus many months ago will not affect current tests. Accordingly we carried out a number of tests involving platelets on 'controls', and on patients with a past history of either myocardial infarction or deep vein thrombosis (DVT) and patients suffering from intermittent claudication who also are assumed to be at higher risk than the controls. Differences were demonstrated between controls and patient groups and these differences were utilized to develop statistical functions with the ability to discriminate between the groups. The functions were then tested using a second set of data from similar groups. Those designed to discriminate between myocardial infarction patients and controls and between patients with claudication and controls were validated. The heparin thrombin clotting time was found to be the prime predictor variable; the platelet count, platelet volume, platelet factor 3 clotting time and the bleeding time have some predictive value. The antithrombin clotting time, platelet aggregation and platelet adhesiveness tests as measured were not found to have discriminating potential. It is suggested that these appropriate risk functions could be of practical value in identifying members of the general population who may be at greater risk than average. The discriminate functions for DVT patients and controls could not be validated, suggesting differences in platelet involvement in arterial and venous thrombosis.
Atherosclerosis 1982 Oct
PMID:Platelets in the prediction of thrombotic risk. 715 92

Twelve patients with varying degrees of peripheral atherosclerotic disease were given an antiaggregatory drug, ticlopidine [5-(6-chlorobenzyl)-4,5,6,7-tetrahydrothieno-(3,2-C)-pyridine HCl] in a single blind trial for one or four months and the effects on platelet aggregation, blood coagulation, marcro- and micro-circulation and walking distance were studied. Two patients were excluded; one because of nausea attributable to the drug, one because of lack of co-operation. No statistically significant changes in circulation parameters or walking distance were noted. No changes were observed in APT-time, thrombine- and Reptilase-clotting time, platelet counts, concentrations of fibrinogen and fibrinopeptide A in plasma or serum antithrombin activity. The mean concentration of fibrinopeptide A was slightly increased in all patients. ADP-induced aggregation was inhibited in all patients. Aggregation induced by arachidonic acid was partially inhibited but not abolished in all patients. Prostaglandin G2-induced aggregation was not altered by ticlopidine but collagen-induced aggregation was inhibited. Ticlopidine, in contrast to acetyl-salicylic acid, inhibits the primary aggregation but also seems to interfere with the release action. Treatment of larger patient groups for longer periods are necessary to determine the clinical usefulness of ticlopidine.
Atherosclerosis 1980 Aug
PMID:Antiaggregatory, physiological and clinical effects of ticlopidine in subjects with peripheral atherosclerosis. 741 66


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