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)

The effect of hyperlipidaemia on endothelial cell haemostatic properties was examined using ex vivo studies on aortic segments obtained from fat-fed Chinchilla rabbits, mounted in a template device which exposed the luminal surface. Exposure of arterial endothelium to lipids resulted in marked enhancement of externally exposed anionic phospholipids, detected using either fluorescence microscopy with the probe merocyanine 540 or by binding of 125I-polymyxin B and 125I-Annexin V. Consistent with the known procoagulant properties of anionic phospholipid, following the lipid and cholesterol-rich diet intake, intact endothelial cells demonstrated enhanced binding of radioiodinated factors IX/IXa and Xa, and enhanced factor IXa/VIII-dependent factor X activation and factor Xa-factor Va-mediated prothrombin activation. Both factor Xa and thrombin formation were blocked, in large part, by polymyxin B, suggesting dependence of the reaction on anionic phospholipids. Consistent with these results, evidence of increased activation of the coagulation mechanism in vivo was observed in hyperlipidaemic animals, as assessed by a three-fold increase in levels of circulating antithrombin-protease complexes, compared with normolipidaemic controls.
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PMID:Intrinsic procoagulant surface induced by hypercholesterolaemia on rabbit aortic endothelium. 829 24

Oversulfated fucoidan fragments (20-40 and 40-60 kDa) were prepared, and their fibrinolytic and anticoagulant activities were compared with those of oversulfated fucoidan (100-130 kDa) reported previously [Soeda et al., Biochem. Pharmacol. 43, 1853-1858, 1992]. The results of these experiments indicated that the in vitro abilities of oversulfated fucoidan to stimulate tissue plasminogen activator (t-PA)-catalyzed plasminogen activation and to potentiate thrombin inhibition by antithrombin III or heparin cofactor II decreased with a decrease in its molecular size. However, the preventive effects of both fucoidan fragments on endotoxin-induced hepatic vein thrombosis in hyperlipemic rats were almost the same as that of oversulfated fucoidan (100-130 kDa). We also found that, unlike heparin treatment, the concentrations of serum and vascular endothelium t-PA in rats treated with oversulfated fucoidan or its fragments (1 mg each/kg/week) were maintained at normal levels. The 20-40 and 40-60 kDa fragments had an ability to decrease the elevated levels of serum cholesterol in hyperlipemic rats, whereas the 100-130 kDa fucoidan derivative did not. These results suggest that oversulfated fucoidan and its fragments have another function(s), besides the regulation of blood coagulation and fibrinolysis, and are of therapeutic benefit for the prevention of thrombus formation in hyperlipemia.
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PMID:Preparation of oversulfated fucoidan fragments and evaluation of their antithrombotic activities. 830 63

Diabetes mellitus and hyperlipidemia are associated with coronary heart disease and with hypercoagulability, another independent risk factor for coronary heart disease. In 65 non-insulin-dependent diabetes mellitus patients [41 females, 24 males, median age 66 years (range 43-81 years)] treated with antidiabetic agents glycometabolic control (HbA1c), lipids (Quetelet index and blood lipids), and several coagulation parameters were studied in comparison with a reference group. Serum triglycerides were elevated [median (interquartile range) 2.3 (1.3) mmol/l vs. 1.6 (0.7) mmol/l in the controls (P < 0.001)], whereas the median lipoprotein(a) concentration was 65 (157) mg/l in the diabetic patients versus 44 (114) mg/l in the control group (not significantly different). Median high-density lipoprotein-cholesterol concentrations were slightly decreased in the diabetic patients: 1.2 (0.3) mmol/l compared with 1.3 (0.4) mmol/l in the control group (P < 0.02). Elevated levels of fibrinogen, fibrin monomers, thrombin-antithrombin III complex, and factor VIIIc were found in the diabetic patients and factor VII in male diabetic patients. These elevated coagulation parameters are indicators of an activated coagulation system in this patient group. By Spearman's rank test, only HbA1c values correlated with anti-thrombin III (r = 0.27, P < 0.03) and showed a tendency towards a correlation with lipoprotein(a) (r = 0.23, P < 0.07). Triglycerides correlated with the Quetelet index (r = 0.27, P < 0.03), high-density lipoprotein-cholesterol (r = -0.41, P < 0.001), and factor VII (r = 0.35, P < 0.01), whereas serum cholesterol concentrations correlated with factor VII (r = 0.27, P < 0.04) and with fibrin monomers (r = 0.29, P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glycometabolic control, lipids, and coagulation parameters in patients with non-insulin-dependent diabetes mellitus. 840 Mar 36

The cardiovascular risk factors blood pressure, overweight, hyperlipidaemia and several coagulation parameters were studied in a group of 54 otherwise healthy patients with essential hypertension of moderate severity. Of the 54 hypertensive patients, 43 were treated with anti-hypertensive drugs and 11 were not. The patients included in this study who were treated with anti-hypertensive drugs were still hypertensive in spite of their treatment. Lipoprotein levels and coagulation parameters did not differ between the untreated and treated hypertensive patients. Substantial percentages of patients were found to have hypertriglyceridaemia (46%), elevated LDL-cholesterol (28%) and elevated lipoprotein(a) concentrations (43%). Coagulation factors F VIIIc, fibrin monomer and factor VII in males were significantly elevated in comparison with a healthy reference group. These data are compatible with a moderate activation of the coagulation system. Correlations were established between systolic blood pressure and serum cholesterol (r = 0.43, p = 0.003), LDL-cholesterol (r = 0.34, p = 0.02) and triglycerides (r = 0.35, p = 0.01); Quetelet-index with fibrinogen (r = 0.37, p = 0.02) and thrombin-antithrombin III (r = 0.30, p = 0.04); and triglycerides with F VIIc (r = 0.34, p = 0.03) and fibrin monomer (r = 0.29, p = 0.04) respectively. These data link hypertension and hyperlipidaemia with increased coagulation activity and may contribute to our understanding of why these two cardiovascular risk factors accelerate atherogenesis.
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PMID:Coagulation factors and lipid composition of the blood in treated and untreated hypertensive patients. 846 17

Mortality rates associated with cardiovascular disease (CVD) are high in long-term dialysis patients. Increased levels of plasma fibrinogen (FBG), coagulation factor VII (FVII), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) as well as hyperlipidemia are regarded as important risk factors for CVD. To investigate whether there are differences in the risk of CVD between chronic hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients, serum lipid levels and plasma FBG, FVII, t-PA, and PAI-1 levels were measured in 17 patients on HD and 17 patients on CAPD. FBG was measured by the thrombin time method, FVII activity (FVIIc) by the chromogenic prothrombin time method, and t-PA and PAI-1 activity by the chromogenic substrate assay. No difference was found in body mass index (BMI) between HD and CAPD patients. Total cholesterol (TC), TC/high-density lipoprotein (HDL)-C ratio, low-density lipoprotein (LDL)-C, and triglycerides (TG) were significantly increased, and HDL-C was significantly decreased in CAPD patients compared with HD patients. FBG and FVIIc were significantly elevated in CAPD patients compared with controls or HD patients. T-PA activities were significantly higher in HD and CAPD patients than in controls. CAPD patients showed significantly higher PAI-1 activities than controls or HD patients. Significant positive correlations were found between FBG or FVIIc and TC, between FBG and LDL-C or TG, and between FVIIc and LDL-C in these patients. T-PA showed significant negative correlations with FBG, PAI-1, TC, LDL-C, and TG. There was a significant positive correlation between PAI-1 and TG and a significant negative correlation between PAI-1 and HDL-C. We conclude that CAPD patients may have a greater risk of CVD than do HD patients, and that coagulation and fibrinolytic activity are correlated with lipid disorders in these patients.
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PMID:Fibrinogen, coagulation factor VII, tissue plasminogen activator, plasminogen activator inhibitor-1, and lipid as cardiovascular risk factors in chronic hemodialysis and continuous ambulatory peritoneal dialysis patients. 865 Dec 50

Multiple cell membrane alterations have been described in humans and animals with various genetic forms of hypertension and/or dyslipidemia. The aim of our study was to characterize some properties of platelets and/or erythrocytes (cytosolic calcium handling, intracellular pH regulation and thrombin responsiveness) in a new model of genetic hypertension associated with hyperlipidemia-Prague hereditary hypertriglyceridemic (HTG) rats. There were no differences in basal cytosolic Ca2+ values in platelets or erythrocytes of HTG rats and control Wistar rats. Ca2+ influx into erythrocytes was also similar in HTG and control rats. In both strains Ca2+ influx correlated positively with plasma triglycerides. The slope of this relationship was less steep in HTG than in Wistar rats. Cytosolic Ca2+ response to thrombin stimulation was smaller in HTG platelets, which were also characterized by a major reduction of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels. Platelets of HTG rats had the same basal intracellular pHi values and similar buffering capacity as control rats but their pHi response to thrombin stimulation was substantially reduced. It can be concluded that reduced responsiveness to thrombin stimulation is a major alteration found in platelets of hypertensive hereditary hypertriglyceridemic rats.
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PMID:Cell calcium handling and intracellular pH regulation in hereditary hypertriglyceridemic rats: reduced platelet response to thrombin stimulation. 876 14

In vitro studies in purified plasma systems have suggested that triglyceride-rich lipoproteins such as chylomicrons, very low density lipoproteins, and their remnants promote activation of factor VII through activated factor XII (XIIa) and the intrinsic coagulation pathway. We specifically examined the roles of factors XII, XI, and IX in activation of factor VII during alimentary lipemia in vivo in humans and addressed the issue of whether generation of activated factor VII (VIIa) is accompanied by increased thrombin production. For this purpose XIIa, factor IX activation peptide (IXP), VIIa, prothrombin fragment 1 + 2 (F1 + 2), and thrombin-antithrombin complex (TAT) were determined in plasma samples taken before and 3, 6, and 9 hours after intake of a mixed meal type of oral fat load in 24 healthy men The VIIa response to fat intake was also determined in 7 patients with single coagulation-factor deficiency, of whom 2 were deficient in factor XII, 2 in factor XI, and 3 in factor IX. Postprandial activation of factors IX and VII occurred in the healthy individuals, whereas the plasma levels of XIIa did not change in response to the test meal. Of note, plasma concentrations of F1 + 2 were unaltered during alimentary lipemia, and TAT levels showed a small decrease (P < .05) in the 3-hour sample compared with the fasting level, indicating that thrombin generation is not stimulated in the postprandial state, despite the generation of activated factor IX (IXa) and VIIa. Factor VIIa increased in the postprandial period in the 2 factor XII-deficient patients who underwent the oral fat tolerance test but appeared to remain unchanged in the factor XI- and factor IX-deficient patients. Therefore, the current concept that activation of factor XII plays a pivotal role in initiating the sequence of events linking postprandial lipemia to activation of factor VII is contradicted by the present study. Whether activation of factor XI by triglyceride rich lipoproteins initiates these reactions needs to be demonstrated in future studies.
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PMID:In vivo demonstration in humans that large postprandial triglyceride-rich lipoproteins activate coagulation factor VII through the intrinsic coagulation pathway. 891 Dec 71

Free radical activity may contribute to atherosclerotic lesions which in diabetic subjects may frequently lead to vascular complications. It is known that oxidative stress is associated to diabetes. Protein glycation and glucose oxidation could be possible source of free radicals. 28 non insulin dependent diabetic subjects (NIDDM) were examined. 20 healthy subjects matched for age, sex and for the presence of hypertension and hyperlipidemia were also studied. Hydrogen peroxide, measured by intracellular levels of the fluorescent 2,7-dichloro-fluorescein (DCF), was considered as indicative parameter of free radical production. The results showed that in resting platelets the basal level of hydrogen peroxide was significantly higher in diabetic subjects than in controls. Moreover, after stimulation with thrombin, collagen, phorbol myristate acetate (PMA) and platelet activating factor (PAF), platelets of diabetic subjects generated significantly higher amounts of hydrogen peroxide than controls. Moreover, platelet aggregation induced by adenosine 5'-diphosphate (ADP) and plasma beta TG levels were higher in diabetics than in controls. In diabetic patients platelet free radical production and functional activity are increased and therefore could play a role in the elevated thrombotic risk described in diabetes.
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PMID:Hyperactivity and increased hydrogen peroxide formation in platelets of NIDDM patients. 917 36

The plasma levels of blood coagulation and fibrinolytic factors and the serum levels of lipids were measured in 62 subjects (22 normolipidemia and 40 hyperlipidemia) to investigate whether hyperlipidemia may affect the hemostatic system. Prothrombin, factors VII, IX and X were elevated in hyperlipidemic patients. The positive correlations were found between factors VII, IX and X, and triglyceride. The significant correlations were also found between VII and IX, and total cholesterol. Plasma levels of thrombin-antithrombin III complex (TAT), which reflects activation of coagulation system, were slightly but significantly higher in type IIb hyperlipidemia, although they were within normal range. Plasma levels of active plasminogen activator inhibitor (PAI) in type IIb and IV were significantly higher than in normals. A significant correlation was found between active PAI and triglyceride (r = 0.76, p < 0.0001). After the administration of fat emulsion to 18 patients with various diseases, which induced artificial hypertriglyceridemia, PAI levels as well as triglyceride levels significantly increased. These results suggest that hypertriglyceridemia may increase the synthesis and/or release of PAI, inducing a hypofibrinolytic condition, which could lead to thrombosis. It has been established that lipoprotein (a) [Lp(a)], which has a molecular structure homology to plasminogen, impairs fibrinolysis by its competitive inhibition of adsorption of plasminogen to vascular endothelial surface and/or fibrin. We assayed plasma levels of Lp(a) and parameters of blood coagulation and fibrinolysis in 168 patients with type II diabetes mellitus and 48 normal controls. In the diabetics, the levels of Lp(a) as well as levels of tissue-type plasminogen activator (t-PA) antigen and PAI activity were significantly higher than normal controls. Furthermore, it was shown that Lp(a) had a weakly negative correlation with t-PA antigen in the diabetics. These results suggest that an elevated level of Lp(a) may decrease release of t-PA, although the underlying mechanism remains unsolved.
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PMID:Hyperlipidemia and hemostatic system. 922 30

The lipolysis of triglyceride-rich lipoproteins may provide a surface that supports the activation of factor XII (FXII) with subsequent activation of factor VII (FVII). Plasma levels of activated FVII (FVIIa) but not activated FXII (FXIIa) are increased in the post-prandial state when there is a transient increase in triglyceride levels. We compared plasma levels of FXIIa antigen in control subjects (n = 33) and in patients with chronically elevated lipids (primary hyperlipidaemia, n = 49), with FVIIa and markers of thrombin generation. Results are given as median (first and third quartiles). Plasma levels of FXIIa [2.34 (1.68-3.32) ng/ml versus 1.53 (0.93-1.86) ng/ml, P = 0.0002], FVIIa [3.02 (2.15-4.64) ng/ml versus 2.20 (1.66-2.56) ng/ml, P = 0.0004], thrombin-antithrombin complexes [3.08 (2.16-5.54) microg/I versus 2.13 (1.46-2.84) microg/l, P = 0.005] and prothrombin fragment 1 + 2 (Pro F1 + 2) [1.28 (1.08-1.50) nmol/l versus 0.92 (0.65-1.08) nmol/l, P = 0.0001] were increased compared with controls irrespective of the type of hyperlipidaemia. In hyperlipdaemic subjects, levels of Pro F1 + 2 were correlated with FVIIa (r = 0.56, P = 0.0002) and FXIIa (r = 0.31, P = 0.03). These results suggest increased activation of both FVII and FXII in hyperlipidaemic subjects, which correlates with increased thrombin generation. Given the lack of correlation between levels of FXIIa and FVIIa, it remains to be established whether the increase in FXIIa is responsible for increased FVIIa activity in this subject group.
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PMID:Plasma levels of factor XIIa and factor VIIa are increased but not related in primary hyperlipidaemia. 1141 32


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