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)

Previously we have shown that incubation of heparinized blood with a low dose of lipopolysaccharides (5 ng/ml) resulted in a 60% higher generation of TxB2 in the blood of young men as compared with that of young women. In the present study, we investigated a group consisting of 38 healthy men and 38 healthy postmenopausal women aged 50-73 years with no drug use and no known chronic disease. In contrast to our earlier observation that young men produce more TxB2 than young women, no significant difference was observed between the men and women when all the participants above 50 years of age were included (5.7 +/- 0.6 ng/l for men versus 5.2 +/- 0.7 ng/l for women). However, a strong correlation was found with simple regression analysis when increasing TxB2 generation was compared with years after menopause (P < 0.0001). No such correlation was observed for increasing age of men and their TxB2 production. The LPS stimulation system of whole blood was also used to evaluate the production of tumor necrosis factor (TNF-alpha) in older people. Men were found to generate 60% more TNF-alpha than women, but no correlation was found between increasing age of women and TNF-alpha production as observed with TxB2. Risk factors such as SDS-cholesterol, fibrinogen and factor VII were the same in men and women, whereas total cholesterol was higher in women than in men (P < 0.05). Since TxA2 is known to be a mediator of atherosclerotic-induced lesions and TNF-alpha is a well-established indicator of inflammatory reactions, we propose that the reduced production of TxB2 and TNF-alpha in women in our model system may partially explain the lower incidence of atherosclerosis in women as compared with men, and the phenomenon of increased incidence of this disease after menopause.
Atherosclerosis 1993 Aug
PMID:Thromboxane production in the blood of women increases after menopause whereas tumor necrosis factor is reduced in women compared with men. 825 57

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.
Atherosclerosis 1993 Nov
PMID:Lipid-related hemostatic abnormalities in the elderly: imbalance between coagulation and fibrinolysis. 829 90

Recent epidemiological evidence indicates that the hemostatic profile is an important predictor of cardiovascular disease, yet its dietary determinants are not well established. An important question is whether dietary fatty acid intake influences blood levels of coagulation proteins. We examined potential dietary determinants of six hemostatic factors--fibrinogen, factor VII, factor (vWF), protein C, and antithrombin III--in four population-based samples totaling over 15,000 participants, blacks and whites, in the Atherosclerosis Risk in Communities (ARIC) Study. Usual dietary intake was assessed by a food frequency questionnaire. Cross-sectional associations were explored using multiple linear regression analysis, adjusting for gender, race, age, body mass index, smoking status, alcohol use, diabetes, and field center. Dietary intake of n-3 polyunsaturated fatty acids (PUFAs) showed negative associations with fibrinogen, factor VIII, and vWF (blacks and whites) and a positive association with protein C (whites only). Fish intake, the major source of dietary n-3 PUFAs, was similarly related to the hemostatic profile: a 1 serving per day greater fish intake was associated with the following predicted differences (95% confidence interval): fibrinogen, -2.9 mg/dL (-6.3, 0.5); factor VIII, -3.3% (-5.4, -1.3); vWF, -2.7% (-5.2, -0.1) (blacks and whites); and protein C, +0.07 microgram/mL (0.03, 0.11) (whites only). Other nutrients or foods were variably associated with the hemostatic factors. These population-based associations, although cross-sectional, suggest that increases in n-3 PUFA intake from fish may modify the blood levels of several coagulation factors.
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PMID:Associations of fish intake and dietary n-3 polyunsaturated fatty acids with a hypocoagulable profile. The Atherosclerosis Risk in Communities (ARIC) Study. 834 95

Six healthy male volunteers were served 4 strictly controlled isoenergetic diets differing in fat (20% or 50% of energy) and fiber contents (2 or 4 g/MJ) for periods of 2 days. The diets were served in random order with at least 5 days separating each diet period. Blood samples for determination of factor VII clotting activity using human (FVIIc) and bovine thromboplastin (FVIIbt), and for assessment of factor VII antigen (FVIIag), tissue-plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, PAI activity, t-PA and euglobulin fibrinolytic activity, and triglyceride and insulin levels were collected regularly on the second day of each diet period. The high-fat diets resulted in significantly increased postprandial FVIIbt levels (peak values: 131% vs. 95%, P < 0.01), and higher postprandial FVIIbt/FVIIag ratios (peak values: 1.42 vs. 1.16, P < 0.01) compared with the low-fat diets. Fibrinolytic variables were not affected by the dietary changes and consistently showed characteristic U-shaped (t-PA and PAI-1 antigen, PAI activity), or inverted U-shaped (t-PA and euglobulin fibrinolytic activity) circadian patterns with troughs and peaks, respectively, at 17:30-21:30 h. The dietary fiber content had no significant influence on any of the measured variables. Our findings indicate that high-fat diets may increase blood thrombogenicity by virtue of augmented postprandial activation of factor VII.
Atherosclerosis 1993 Jul
PMID:Dietary effects on circadian fluctuation in human blood coagulation factor VII and fibrinolysis. 839 16

It has been shown that triglyceride levels are one of the determinants of factor VII levels. In this study we have simultaneously evaluated, in a group of 102 healthy individuals, the different forms of factor VII, namely factor VII mass, factor VII coagulant activity, activated factor VII double-chain form and factor VII-phospholipid complex, in relation to triglyceridaemia. The data showed a highly significant correlation of factor VII mass, factor VII coagulant activity and factor VII-phospholipid complex with triglycerides. No correlation was observed between the activated factor VII double-chain form and triglycerides. These data, together with analysis of the linear and orthogonal regression slopes, suggest that increase of plasma factor VII coagulant activity as a function of plasma triglyceride levels is attributable to an increase in both mass and activity of factor VII and that the increase in activity is dependent on an increase of factor VII-phospholipid complex rather than activated factor VII double-chain form. The ratio between the slopes of the regression straight line of factor VII mass and factor VII-phospholipid complex in relation to triglycerides was 2.23 (95% confidence limits 1.74-2.50), thus indicating that the contribution of factor VII mass is prevalent over that of the factor VII-phospholipid complex.
Atherosclerosis 1993 Feb
PMID:Levels of plasma factor VII and factor VII activated forms as a function of plasma triglyceride levels. 846 Oct 60

Plasma factor VII activity (FVIIc) is one of the independent risk factors of coronary artery disease (CAD) and is controlled by both genetic and environmental factors. South Asians including Indians have one of the highest prevalence and mortality rates from CAD while the Chinese have a much lower risk. Generally accepted risk factors cannot explain the high mortality from CAD in Indians. We examined two hundred and seventy seven Chinese (124 m, 153 f); and 216 healthy Indian (150 m, 66 f) adults for serum lipids; plasma FVIIc and FVIIag levels in order to examine racial variations of these and their correlates in these two populations. Both Indian men and women had significantly higher FVIIc levels (12% and 11%, respectively) than the Chinese even after adjustments of age, BMI and lipids (P < 0.01). In contrast, Indians had significantly lower plasma FVIIag levels than Chinese (8% and 9%, respectively in men and women; P < 0.01). Multiple linear regression analysis shows a strong correlation of FVIIc with serum triglycerides accounting for 4-8% of the total variability of FVIIc in different groups. Further, there was a stronger correlation between FVIIc and FVIIag in Indians than that in the Chinese (0.43 vs. 25) suggesting a greater activation resulting in higher FVIIc in Indians inspite of lower FVIIag levels. The higher FVIIc and stronger activation by triglycerides observed in this study partly explain the higher risk of CAD in Indians.
Atherosclerosis 1995 Sep
PMID:Racial variation of factor VII activity and antigen levels and their correlates in healthy Chinese and Indians at low and high risk for coronary artery disease. 854 53

Several haemostatic factors have been shown to have a predictive role in cardiovascular disease, although their relationship with prevalent peripheral arterial disease is not well reported. Using a random sample of 1592 men and women aged 55-74 years from Edinburgh, Scotland, we examined the relationship of von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and fibrin D-dimer antigens and factor VII activity to peripheral arterial disease. t-PA antigen and fibrin D-dimer showed significant linear trends of increased levels with increasing severity of disease in both sexes (p < or = 0.01) and vWF showed a similar pattern in men only (p < or = 0.01). On multivariate analysis, fibrin D-dimer was independently related to the risk of intermittent claudication (p < or = 0.01) and, among men, to the extent of arterial narrowing in the lower limb, as measured by the ankle brachial pressure index, (ABPI) (p < or = 0.001). These results are further evidence of a role for intravascular fibrin deposition in the development of peripheral atherosclerosis.
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PMID:Fibrin D-dimer, haemostatic factors and peripheral arterial disease. 857 5

Tissue factor, a member of the cytokine-receptor superfamily and high-affinity receptor and cofactor for plasma factor VII/VIIa (ref. 1), is the primary cellular initiator of blood coagulation. It is involved in thrombosis and inflammation associated with sepsis, atherosclerosis and cancer, and can participate in other cellular processes including intracellular signalling, metastasis, tumor-associated angiogenesis, and embryogenesis. Here we report that inactivation of the tissue factor gene (TF) results in abnormal circulation from yolk sac to embryo beyond embryonic day 8.5, leading to embryo wasting and death. Vitelline vessels from null mice were deficient in smooth-muscle alpha-actin-expressing mesenchymal cells, which participate in organization of the vessel wall. This implies that tissue factor has a role in blood vessel development.
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PMID:Role of tissue factor in embryonic blood vessel development. 877 17

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

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


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