Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inbred Carworth Farms Nelson (CFN) congenitally hyperlipidemic rats had significantly shorter coagulation and prothrombin times and higher levels of coagulation factors, II, V, VII, VIII, and X than did controls. Conversely, congenitally hypolipidemic rats of the same strain had significantly longer coagulation and prothrombin times and lower levels of factors II, V, VII, X and XII and of blood platelets than did controls. A loop-shaped polyethylene cannula was inserted into the aorta to assess the potential for thrombosis. The hyperlipidemic group obstructed this significantly faster and the hypolipidemic group slower than did the controls. Normal CFN rats made hypertensive by unilateral renal artery clip developed hypertension together with significantly elevated serum cholesterol and factor VII and X levels. Rhesus monkeys with diet-induced hyperlipidemia showed shorter prothrombin times and higher factor X levels than did controls on normal diet. By selective breeding, two groups of squirrel monkeys were obtained. Both groups had similar serum cholesterol levels on a normal diet but one group (hyperresponders) showed higher serum cholesterol levels on a cholesterol-containing diet than did the other (hyporesponder) group. Both groups showed significantly elevated levels of factors II, V, VII, IX and X on a cholesterol-containing diet. There was good correlation between the levels of many coagulation factors and serum cholesterol in both rats and monkeys. If thrombosis is important in the genesis of atherosclerosis, these findings could indicate that elevation of plasma lipids may play a role, via the coagulation pathway, in the production of human vascular disease.
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PMID:Hyperlipidemia, hypercoagulability, and accelerated thrombosis: studies in congenitally hyperlipidemic rats and in rats and monkeys with induced hyperlipidemia. 81 75

In the 1970s in the Diet-Antismoking Trial, of the Oslo Study, colleagues and I found that the majority of high-risk men with elevated serum cholesterol and elevated triglyceride concentrations had impaired fibrinolytic capacity. Later on, both our group and others found a similar negative correlation between serum triglyceride levels and fibrinolytic capacity. Furthermore, in a prospective study of dietary intervention in individuals with both elevated cholesterol and triglyceride levels, we found that dietary lowering of serum triglyceride levels was significantly and positively correlated with an improvement in fibrinolytic capacity. In another study, we made the same observation for the coagulation factor VII-phospholipid complex: the more the triglycerides were reduced by diet, the greater was the change in factor VII complex. This correlation was highly significant and independent of changes in serum cholesterol. Platelet function is also influenced by dietary habits, but except for the effects of a fish oil-enriched diet, few data are available about the dietary effects on platelet function. It seems, however, that in individuals with elevated lipid levels and elevated blood pressure, increased platelet reactivity is a highly prevalent finding. Many of the hemostatic risk variables are associated with the so-called "metabolic risk syndrome" characterized by an increase in serum insulin level, together with increased relative body weight, mild hypertension, hyperlipidemia, and physical inactivity. This syndrome can often be influenced favorably by life-style changes. A controlled study with interventions in diet and activity level has just been started by our group.
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PMID:The influence of dietary change on hemostatic risk variables. 134 3

A high factor VII coagulant activity (VIIc), a marker of increased risk of coronary heart disease, is frequently found in types IIb and IV hyperlipidaemia, but its cause is not fully understood. Factor VII can be activated by factor XIIa, generated from factor XII upon activation of the contact system of coagulation. Ten patients with familial lipoprotein-lipase (LPL) deficiency and 10 healthy control subjects were therefore compared to explore the hypothesis that high concentrations of unesterified fatty acids (UFA), released from triglyceride-rich lipoproteins by LPL, are a source of factor XII activation and hence the increased VIIc that is observed post-prandially and in non-LPL-deficient hypertriglyceridaemic states. Mean plasma cholesterol and triglyceride concentrations were, respectively, 1.5- and 19-fold higher in the patients than controls, due to increases in very-low-density lipoproteins and chylomicrons. The concentration and composition of plasma UFA were similar in both groups. In conformity with the hypothesis, VIIc was not increased in the LPL-deficient group, despite their massive hypertriglyceridaemia. Furthermore, when the patients' plasma was treated with LPL, factor XII was activated promptly and substantially, whereas no similar effect was observed in the controls. These results suggest that high concentrations of circulating triglyceride-rich lipoproteins will increase VIIc in the presence of LPL.
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PMID:Lipolysis of triglyceride-rich lipoproteins activates coagulant factor XII: a study in familial lipoprotein-lipase deficiency. 141 87

There is evidence that increased reactivity of blood plasma to thrombogenic surfaces (hypercoagulability) may contribute to the risk of thrombotic occlusion of a coronary artery in coronary heart disease. The Northwick Park Heart Study found raised levels of factor VII coagulant (VIIc) activity and fibrinogen in men at high risk of a coronary event. Several other European studies have confirmed the latter finding, but the Northwick Park Heart Study is the only study to report formally on VIIc to date. Plasma VIIc is increased in the presence of hyperlipidemia and on a high fat diet, and falls with lipid-lowering therapy and a reduction in fat intake. Fibrinogen concentration is raised in smokers and decreases when the habit is given up. Thus, these markers of thrombogenic risk are readily controlled by standard preventive measures against coronary heart disease. Unresolved issues include: (1) whether the distinctive features of the Northwick Park VII bioassay improve the value of VIIc as a predictor of coronary heart disease; (2) the separate extent to which activation of factor VII and increases in factor VII concentration account for the raised VIIc in hyperlipidemia; (3) the basis of the raised fibrinogen in men at high coronary heart disease risk, even among nonsmokers; and (4) the usefulness of plasma levels of activation peptides of factors IX, X, and prothrombin as markers of thrombogenic risk.
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PMID:Hemostasis and cardiovascular risk. The British and European experience. 145 78

We investigated whether or not obesity is related to increased factor VII activity. We studied 70 obese subjects (aged 25 to 50 years, 25 males and 45 females, body mass index (BMI): mean +/- SD = 32.44 +/- 5.44) and 33 non-obese subjects (aged 25 to 50 years, 12 males and 21 females, BMI: mean +/- SD = 21.80 +/- 1.70). None of them were smokers or affected by hyperlipidemia, diabetes mellitus, impaired glucose tolerance or arterial hypertension. Factor VII activity was measured by the coagulometric method. We found higher factor VII activity in obese subjects (115.74 +/- 26.10%) than in healthy subjects (98.55 +/- 23.49%, p less than 0.005). Increased factor VII levels could determine a thrombophilic state involved in the genesis of cardiovascular accidents in obesity.
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PMID:[Factor VII and cardiovascular risk in obese subjects]. 224 59

An increase in factor VII coagulant activity (FVIIc) was found in patients with high thrombotic risk and in hyperlipidemias, namely in Fredrickson's types IIb and IV. This elevation was correlated with the level of total cholesterol and triglyceride concentrations. It has been suggested that this increase is due to higher FVII coagulant activity related to the formation of a complex between factor VII (FVII) and phospholipids, since it was shown that FVIIc returns to normal levels after incubation of plasma with phospholipase C. In this respect we have studied the activity of FVII before and after phospholipase C plasma treatment and FVII related antigen (FVIIag) in patients with types IIa, IIb and IV hyperlipidemias. An elevation of FVIIc was found in hyperlipidemic patients compared to normal controls. FVIIag values were also higher in type IV patients, implicating an increase in FVII total concentration and not only an activation of FVII. Furthermore, Phospholipase C action on patients' plasma samples lowered FVIIc to levels very similar to those of FVIIag. In normal controls the same action was noted and it seems therefore likely that the proposed phospholipid contribution to FVIIc hyperactivity plays only a minor role in FVII changes in primary hyperlipidemia. Instead, FVIIag increase seems to be the major mechanism of FVII increase in primary hypertriglyceridemic patients.
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PMID:Phospholipase C sensitive FVII activity and FVII antigen in hypertriglyceridemia. 291 18

Intact arterial vessel wall is not thrombogenic. Disorders of the endothelium in connection with pathological coditions such such as atherosclerosis, hyperlipidaemia, hypertension and hyperuricemia induce interaction of surfaces of high thromboplastic activity with the blood stream. In such situations local formation of thrombin will take place immediately. Evidence is presented for the essential and unique activation of the extrinsic pathway of the plasmatic coagulation system. The local formation of thrombin at pathologically altered arterial wall seems to be an important trigger for arterial thrombosis and haemostasis. It could be that in vivo the initial step of thrombogenesis depends upon the formation of the activator complex between tissue-thromboplastin and factor VII.
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PMID:Thromboplastic activity of human arterial walls and its interaction with the plasmatic coagulation system. 744 Nov 81

Tissue factor pathway inhibitor (TFPI) activity was quantified in two cohorts of young male post-infarction patients and in population-based control subjects to explore the relationships between TFPI activity and plasma lipoproteins and to address the issue of coordinate regulation of factor VII and TFPI in hyperlipidaemia and premature coronary heart disease (CHD). Participants were investigated in the fasting state and after an oral fat load. Basal TFPI activity and factor VII antigen (VIIag) levels were found to be increased in the patients (TFPI activity 1.25 +/- 0.23 vs 1.17 +/- 0.20 U/ml, p < 0.05; VIIag 537.7 +/- 127.7 vs 479.4 +/- 93.4 ng/ml, p < 0.001). The parallel increase was accounted for by patients with hypertriglyceridaemic lipoprotein phenotypes. In contrast, the level of activated factor VII (VIIa) neither differed significantly between patients and controls, nor between patients with different lipoprotein phenotypes. The elevated TFPI activity in the patients was closely associated with the plasma level of dense low density lipoprotein (LDL) particles (r = 0.46, p < 0.001) and with the plasma concentration of the small, dense high density lipoprotein (HDL) subspecies HDL3b (r = 0.34, p < 0.01).
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PMID:Relationship of tissue factor pathway inhibitor activity to plasma lipoproteins and myocardial infarction at a young age. 797 36

Dietary studies have established a connection between plasma lipoproteins and coagulation factor VII. The present study was undertaken to specifically examine whether factor VII is activated during alimentary lipemia and to investigate the relations of factor VII mass and activity state with fasting and postprandial lipoproteins and free fatty acids (FFAs). Factor VII levels were therefore determined in plasma samples taken before and after intake of a standardized, oral fat load of a mixed-meal type in 33 men (mean age +/- SD, 48.8 +/- 3.2 years) with a previous myocardial infarction at a young age and 10 healthy, age-matched control subjects. A panel of methods for factor VII determination was used to ensure that changes in all potentially existing forms of the factor during alimentary lipemia would be included. Substantial activation of factor VII was found to occur during alimentary lipemia, whereas the number of factor VII molecules remained constant or even appeared to decrease after the test meal. Activation of factor VII was more pronounced in control subjects than patients, and the proportion of activated factor VII molecules was higher in control subjects. Interestingly, factor VII activation, which correlated quantitatively with the degree of postprandial triglyceridemia, seemed to be related to FFA production during lipolysis of triglyceride-rich lipoproteins that were generated in response to fat intake. Postheparin plasma lipoprotein lipase activity was lower in patients, which could offer one explanation why factor VII activity was lower during alimentary lipemia in these subjects despite their exaggerated postprandial triglyceridemia. Thus, activation of coagulation factor VII during alimentary lipemia may result in a procoagulant state that is likely to promote the formation of a coronary thrombus in individuals with established coronary artery disease.
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PMID:Activation of coagulation factor VII during alimentary lipemia. 827 79

To clarify age-related and lipid-related hemostatic abnormalities in the elderly, we measured the plasma levels of active PAI-1 antigen (aPAI-1), tPA-PAI-1 complex (TPC), plasminogen, alpha 2-plasmin inhibitor (alpha 2-PI), plasmin-alpha 2-PI complex (PIC), and D-dimer, together with the plasma levels of fibrinogen, factor VII (F VII), and thrombin-antithrombin III complex (TAT) and the serum lipid levels in 68 hyperlipidemic and 82 normolipidemic elderly subjects. The aPAI-1 ratio was calculated as aPAI-1/(aPAI-1 + TPC). In the normolipidemic elderly subjects, plasma PIC and D-dimer levels were much higher when compared with healthy young controls, and there was also a decrease in plasma plasminogen and alpha 2-PI levels, an increase in plasma TPC levels, and high plasma F VII and fibrinogen levels. In elderly subjects with type IIb hyperlipidemia, both the plasma aPAI-1 level and the aPAI-1 ratio were significantly increased, while the plasma PIC and D-dimer levels were reduced despite higher plasma F VII, fibrinogen and TAT levels. Both serum total cholesterol and triglyceride levels were correlated positively with plasma F VII and TAT levels and with the TAT/PIC ratio, while only serum triglyceride levels showed a positive correlation with plasma TPC and aPAI-1 levels and with the aPAI-1 ratio. Thus, an increase of fibrinolytic activity appears to occur as part of normal aging to balance the increase of procoagulant activity. However, an imbalance between thrombin activity (increased procoagulant activity) and plasmin activity (hypofibrinolysis) appears to occur in elderly individuals with hyperlipidemia, perhaps resulting in a predisposition to thromboembolic disease.
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PMID:Lipid-related hemostatic abnormalities in the elderly: imbalance between coagulation and fibrinolysis. 829 90


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