INCREASED FACTOR VII REACTIVITY IN THE RABBIT FOLLOWING DIET-INDUCED HYPERCHOIESTEROIAEMIA

1987 ◽  
Author(s):  
K A Mitropoulos ◽  
S J Walter ◽  
T W Meade ◽  
M P Esnouf
Keyword(s):  
Plasma Cholesterol ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Fold Increase ◽  
Plasma Lipoproteins ◽  
Cholesterol Concentration ◽  
Factor Vii ◽  
Standard Diet ◽  
Factor X ◽  
Single Chain

The association of factor VII coagulant activity (VIIC) with plasma lipid concentrations has been a consistent feature of a number of studies in man and points to plasma lipoproteins as determinants of VIIC.To modify plasma lipoprotein concentrations and to study the effect of this on VIIC, rabbits were fed a 1%- cholesterol-supplemented diet. Treatment resulted in a many-fold increase in plasma cholesterol concentration with the major fraction of excess cholesterol associated with the very low and intermediate density lipoprotein fractions. VIIC was considerably higher in rabbits fed 1%- cholesterol-supplemented than in rabbits fed the standard diet. In both groups of rabbits, the direction and extent of variation in VIIC coincided with variation in cholesterol concentration so that over time there were significant and positive correlations between VIIC and plasma cholesterol. A method that provides a measure of the total functionalfactor VII concentration (VII) was also used. This assay involves clotting the plasma in the presence of excess tissue factor and therefore the conversion of VII tothe more reactive two-chain form of theprotein (αVIIa) .The concentration of αVIIa present in the serum was measured from the rate of activation of excess of [sialyl-3H]-bovine factor X. By day 10 of treatment, and in all furthercomparisons VTIt was only slightly higher in the group of rabbits fed cholesterol-supplemented than in that fed the standard diet.This increase in VI11 istoo small to explain the considerable increasin VIIC in the hypercholesterolaemic rabbit. We conclude thattheincrease in VIIc was to ahigher proportion of αVIIa in theplasma of hyperchol⋆esterol-aemic rabbits rather thanto an increase in the concentration of the single-chain protein.

scholarly journals Role of the liver in low-density-lipoprotein catabolism in the rat

1984 ◽  
Vol 220 (1) ◽  
pp. 333-336 ◽  
Author(s):  
S Bhattacharya ◽  
S Balasubramaniam ◽  
L A Simons
Keyword(s):  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Fold Increase ◽  
Hepatic Uptake ◽  
Linear Increase ◽  
Cholesterol Concentration ◽  
Synthesis Rate ◽  
Low Density ◽  
Oestradiol Treatment

Plasma low-density-lipoprotein (LDL) kinetics and hepatic LDL uptake were studied in the rat after an intravenous pulse injection of [14C]sucrose-labelled LDL. Some 96% of injected radioactivity was associated with apoprotein B of LDL (d 1.020-1.050). The disappearance of labelled LDL from plasma was accompanied by a linear increase in the hepatic uptake of LDL, up to 12 h after injection. Oestradiol treatment lowered plasma cholesterol concentration by 58% and the intravascular pool of LDL by 78%. This was associated with a 4-fold increase in the fractional catabolic rate of LDL and a 2-fold increase in the hepatic uptake of LDL. Oestradiol treatment did not significantly change the synthesis rate of LDL; it decreased the skin and lung uptake of LDL, but increased adrenal uptake. These results suggest that the liver plays an important role in the regulation of plasma LDL concentration.

Plasma Lipid and Lipoprotein Abnormalities in Patients with Malabsorption

1973 ◽  
Vol 45 (5) ◽  
pp. 583-592 ◽  
Author(s):  
Gilbert R. Thompson ◽  
J. Paul Miller
Keyword(s):  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Plasma Lipoproteins ◽  
Low Density ◽  
Cholesterol Levels ◽  
Lipids And Lipoproteins

1. Plasma lipids and lipoproteins have been studied in control subjects and patients with various types of steatorrhoea. 2. Low plasma cholesterol levels were found in malabsorbers and were associated with decreased amounts of low-density lipoprotein (LDL) in males and high-density lipoprotein (HDL) in females. 3. Serum triglyceride levels were normal in males, but exceeded control values in some of the females, due to an increase in very-low-density lipoprotein. 4. LDL composition was abnormal in both male and female malabsorbers, with a decreased proportion of cholesterol ester and an increased proportion of triglyceride. There was also an increased proportion of triglyceride in HDL. 5. These findings show that malabsorption markedly influences not only the concentration but also the composition of plasma lipoproteins.

Plasma Lipoproteins, Hemostasis and Thrombosis

2001 ◽  
Vol 86 (07) ◽  
pp. 386-394 ◽  
Author(s):  
José Fernández ◽  
Hiroshi Deguchi ◽  
John Griffin
Keyword(s):  
Low Density Lipoprotein ◽  
Activated Protein C ◽  
Density Lipoprotein ◽  
Plasma Lipoproteins ◽  
Factor Vii ◽  
Factor X ◽  
Factor Va ◽  
Antithrombotic Effects ◽  
Lipids And Lipoproteins ◽  
Plasma Factors

SummaryRegulation of hemostasis and thrombosis involves numerous plasma factors that contribute to procoagulant and anticoagulant pathways. Lipid-containing surfaces provide sites where both procoagulant and anticoagulant enzymes, cofactors and substrates are assembled to express their activities. Plasma and lipoproteins can contribute to either procoagulant or anticoagulant reactions. Procoagulant lipids/lipoproteins include triglyceride-rich particles in plasma and oxidized low density lipoprotein (LDL) which can accelerate activation of prothrombin, factor X and factor VII. Potentially anticoagulant lipids and lipoproteins, each of which enhances inactivation of factor Va by activated protein C, include phosphatidylethanolamine, cardiolipin, the neutral glycosphingolipids glucosylceramide and Gb3 ceramide (CD77), and high density lipoprotein (HDL). Remarkably, treatment of hyperlipidemia with statins not only lowers lipids but also provides antithrombotic effects whose mechanisms remain to be clarified. We hypothesize that procoagulant and anticoagulant lipids and lipoproteins in plasma may contribute to a Yin-Yang balance that helps influence the up-regulation and down-regulation of thrombin generation.

scholarly journals The Marine Microalga, Tisochrysis lutea, Protects against Metabolic Disorders Associated with Metabolic Syndrome and Obesity

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 430
Author(s):  
Claire Mayer ◽  
Léo Richard ◽  
Martine Côme ◽  
Lionel Ulmann ◽  
Hassan Nazih ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Metabolic Disorders ◽  
Disease Risk ◽  
Plasma Cholesterol ◽  
Cardiovascular Disease Risk ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Standard Diet ◽  
Metabolic Disturbances ◽  
Tisochrysis Lutea

Long-chain polyunsaturated fatty acids n-3 series and especially docosahexaenoic acid are known to exert preventive effects on metabolic disturbances associated with obesity and decrease cardiovascular disease risk. n-3 LC-PUFAs are mainly consumed in the form of fish oil, while other sources, such as certain microalgae, may contain a high content of these fatty acids. The aim of this study was to evaluate the effects of Tisochrysis lutea (Tiso), a microalga rich in DHA, on metabolic disorders associated with obesity. Three male Wistar rat groups were submitted for eight weeks to a standard diet or high-fat and high fructose diet (HF), supplemented or not with 12% of T. lutea (HF-Tiso). The supplementation did not affect plasma alanine aminotransferase (ALAT). Bodyweight, glycemia and insulinemia decreased in HF-Tiso rats (ANOVA, p < 0.001), while total plasma cholesterol, high-density lipoprotein-cholesterol (HDL-C) increased (ANOVA, p < 0.001) without change of low-density lipoprotein-cholesterol (LDL-C) and triacylglycerol (TAG) levels. Tiso supplementation decreased fat mass and leptinemia as well as liver TAG, cholesterol and plasma tumor necrosis factor-alpha levels (ANOVA, p < 0.001) while it did not affect interleukin 6 (IL-6), IL-4 and lipopolysaccharides levels. HF-Tiso rats showed an increase of IL-10 level in abdominal adipose tissue (ANOVA, p < 0.001). In conclusion, these results indicated that DHA-rich T. lutea might be beneficial for the prevention of obesity and improvement of lipid and glucose metabolism.

Performance of commercially-available cholesterol self-tests

2021 ◽  
pp. 000456322199239
Author(s):  
Steef Kurstjens ◽  
Eugenie Gemen ◽  
Selina Walk ◽  
Tjin Njo ◽  
Johannes Krabbe ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Diagnostic Performance ◽  
Plasma Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Cholesterol Concentration ◽  
Limited Information ◽  
Plasma Cholesterol Concentration ◽  
Lipid Panel ◽  
Better Regulation

Background Hypercholesterolemia (plasma cholesterol concentration ≥5.2 mmol/L) is a risk factor for cardiovascular disease and stroke. Many different cholesterol self-tests are readily available at general stores, pharmacies and web shops. However, there is limited information on their analytical and diagnostic performance. Methods We included 62 adult patients who required a lipid panel measurement (cholesterol, high-density lipoprotein (HDL), triglycerides and LDLcalc) for routine care. The performance of five different cholesterol self-tests, three quantitative meters ( Roche Accutrend Plus, Mission 3-in-1 and Qucare) and two semi-quantitative strip tests ( Veroval and Mylan MyTest), was assessed according to the manufacturers’ protocol. Results The average plasma cholesterol concentration was 5.2 ± 1.2 mmol/L. The mean absolute relative difference (MARD) of the five cholesterol self-tests ranged from 6 ± 5% ( Accutrend Plus) to 20 ± 12% ( Mylan Mytest). The Accutrend Plus cholesterol meter showed the best diagnostic performance with a 92% sensitivity and 89% specificity. The Qucare and Mission 3-in-1 are able to measure HDL concentrations and can thus provide a cholesterol:HDL ratio. The Passing-Bablok regression analyses for the ratio showed poor performance in both self-tests ( Mission 3-in-1: y = 1.62x–1.20; Qucare: y = 0.61x + 1.75). The Accutrend Plus is unable to measure the plasma high-density lipoprotein concentration. Conclusions/interpretation: The Accutrend Plus cholesterol meter (Roche) had excellent diagnostic and analytic performance. However, several of the commercially-available self-tests had considerably poor accuracy and diagnostic performance and therefore do not meet the required qualifications, potentially leading to erroneous results. Better regulation, standardization and harmonization of cholesterol self-tests is warranted.

scholarly journals Hypertriglyceridemia and Lower LDL Cholesterol Concentration in Relation to Apolipoprotein E Phenotypes in Myotonic Dystrophy

1989 ◽  
Vol 16 (1) ◽  
pp. 129-133 ◽  
Author(s):  
Sital Moorjani ◽  
Daniel Gaudet ◽  
Claude Laberge ◽  
Marie Christine Thibault ◽  
Jean Mathieu ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Ldl Cholesterol ◽  
Plasma Cholesterol ◽  
Plasma Lipid ◽  
Cholesterol Concentration ◽  
Plasma Triglycerides ◽  
Ldl Particles ◽  
Vldl Cholesterol ◽  
Apo E

ABSTRACT:Plasma lipid, lipoprotein levels and apolipoprotein apo E phenotypes were determined in 70 patients with myotonic dystrophy (MyD) and 81 controls. Marked differences were noticed in the apo E phenotype frequencies between the two groups. Plasma triglycerides and VLDL cholesterol were higher in MyD than controls, but only the latter was related to differences in the apo E phenotypes between two groups. Accordingly, the ratio of VLDL cholesterol/plasma triglycerides was increased significantly in MyD, suggesting accumulation of intermediary density particles due to lower affinity of E2 containing lipoproteins for lipoprotein cell receptors. The LDL cholesterol concentration was lower in MyD than controls and was related to differences in the apo E phenotype frequencies between the two groups. These results indicate increased removal of LDL particles in the apo E2 phenotypes, perhaps due to upregulation of LDL (B, E) receptor activity. Plasma cholesterol and HDL cholesterol concentrations were similar in both groups. Another feature of the study was lower levels of plasma cholesterol, triglycerides, VLDL and LDL cholesterol in the homozygous E4:E4 phenotype. These results suggest increased clearance rate of both VLDL and LDL particles and support the concept that apo E4-containing lipoproteins have higher in vivo affinity for ape E and/or B, E receptors.

Plasma lipoprotein profiles of normocholesterolemic and hypercholesterolemic homozygotes for apolipoprotein E2(Arg158-->Cys) compared

1994 ◽  
Vol 40 (8) ◽  
pp. 1559-1566 ◽  
Author(s):  
S P Zhao ◽  
A H Smelt ◽  
A M Van den Maagdenberg ◽  
A Van Tol ◽  
T F Vroom ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plasma Lipoprotein ◽  
Cholesterol Concentration ◽  
Low Density ◽  
Plasma Cholesteryl Ester ◽  
Familial Dysbetalipoproteinemia ◽  
Lipoprotein Profiles

Abstract We compared plasma lipoprotein profiles of 15 individuals with normocholesterolemic (plasma cholesterol 4.81 +/- 0.90 mmol/L) familial dysbetalipoproteinemia (NFD) and 15 patients with hypercholesterolemic (plasma cholesterol 10.61 +/- 2.32 mmol/L) familial dysbetalipoproteinemia (HFD), matched for age and sex. All subjects were homozygous for apoE2(Arg158--&gt;Cys). Compared with 15 normolipidemic controls (plasma cholesterol 5.47 +/- 0.92 mmol/L), subjects with NFD and HFD had greater cholesterol concentrations of large very-low-density lipoprotein (VLDL1), small VLDL (VLDL2), and intermediate-density lipoprotein, each of which was correlated to their plasma total cholesterol concentration. VLDL1 and VLDL2 subfractions were enriched in cholesteryl ester, and plasma cholesteryl ester transfer protein activities were increased in both NFD and HFD; however, absolute changes were larger in HFD than in NFD. Concentrations of low-density lipoprotein cholesterol were lower in HFD (1.89 +/- 0.48 mmol/L) and NFD (1.56 +/- 0.36 mmol/L) than in normolipidemic controls (3.35 +/- 0.73 mmol/L). We conclude that all subjects homozygous for apoE2(Arg158--&gt;Cys) show features of dysbetalipoproteinemia.

Absence of focal glomerulosclerosis in aging analbuminemic rats

1992 ◽  
Vol 262 (6) ◽  
pp. R947-R954 ◽  
Author(s):  
C. K. Fujihara ◽  
D. M. Limongi ◽  
H. C. De Oliveira ◽  
R. Zatz
Keyword(s):  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Wall Stress ◽  
Plasma Triglyceride ◽  
Sprague Dawley ◽  
Platelet Aggregability ◽  
Sd Rats ◽  
Glomerular Hypertension

The Nagase analbuminemic rat (NAR), a mutant of the Sprague-Dawley (SD) strain, exhibits high levels of plasma cholesterol (Chol), thrombocytosis, and enhanced platelet aggregability, which might promote glomerulosclerosis (GS). To determine whether NAR are more susceptible than SD rats to aging GS, young (3-mo-old) and aging (18-mo-old) SD rats and NAR were studied. In young NAR, glomerular pressure and glomerular volume were lower, whereas total and high-density lipoprotein plasma Chol levels were higher than in young SD rats. Aging SD rats developed glomerular hypertension and hypertrophy. Less glomerular enlargement and subnormal glomerular pressures were seen in aging NAR. Enhanced platelet aggregation developed in aging SD rats, approaching the values seen in NAR. Similarly elevated levels of low-density lipoprotein Chol were seen in additional SD rats and NAR studied at 12 mo of age. Plasma triglyceride (TG) levels were lower in NAR at this age. Only SD rats developed proteinuria and exhibited GS and glomerular lipid deposits at 18 mo of age. Reduced glomerular wall stress due to lower glomerular pressure and volume as well as lower TG levels may explain the absence of GS in aging NAR despite plasma lipid and platelet abnormalities.

scholarly journals The contributions of Ca2+, phospholipids and tissue-factor apoprotein to the activation of human blood-coagulation factor X by activated factor VII

1990 ◽  
Vol 265 (2) ◽  
pp. 327-336 ◽  
Author(s):  
V J J Bom ◽  
R M Bertina
Keyword(s):  
Tissue Factor ◽  
Blood Coagulation ◽  
Reaction Rate ◽  
Factor Viia ◽  
Coagulation Factor ◽  
Fluid Phase ◽  
Fold Increase ◽  
Factor Vii ◽  
Factor X ◽  
Extrinsic Pathway

In the extrinsic pathway of blood coagulation, Factor X is activated by a complex of tissue factor, factor VII(a) and Ca2+ ions. Using purified human coagulation factors and a sensitive spectrophotometric assay for Factor Xa, we could demonstrate activation of Factor X by Factor VIIa in the absence of tissue-factor apoprotein, phospholipids and Ca2+. This finding allowed a kinetic analysis of the contribution of each of the cofactors. Ca2+ stimulated the reaction rate 10-fold at an optimum of 6 mM (Vmax. of 1.1 x 10(-3) min-1) mainly by decreasing the Km of Factor X (to 11.4 microM). In the presence of Ca2+, 25 microM-phospholipid caused a 150-fold decrease of the apparent Km and a 2-fold increase of the apparent Vmax. of the reaction; however, both kinetic parameters increased with increasing phospholipid concentration. Tissue-factor apoprotein contributed to the reaction rate mainly by an increase of the Vmax., in both the presence (40,500-fold) and absence (4900-fold) of phospholipid. The formation of a ternary complex of Factor VIIa with tissue-factor apoprotein and phospholipid was responsible for a 15 million-fold increase in the catalytic efficiency of Factor X activation. The presence of Ca2+ was absolutely required for the stimulatory effects of phospholipid and apoprotein. The data fit a general model in which the Ca2(+)-dependent conformation allows Factor VIIa to bind tissue-factor apoprotein and/or a negatively charged phospholipid surface resulting into a decreased intrinsic Km and an increased Vmax. for the activation of fluid-phase Factor X.

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