Effect of simvastatin on plasma lipid and lipoprotein concentrations and low-density lipoprotein metabolism in the nephrotic syndrome

1992 ◽  
Vol 82 (6) ◽  
pp. 701-708 ◽  
Author(s):  
G. L. Warwick ◽  
C. J. Packard ◽  
L. Murray ◽  
D. Grierson ◽  
J. P. Stewart ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Apolipoprotein B ◽  
Cholesterol Synthesis ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Cholesterol Concentration ◽  
Low Density ◽  
Coa Reductase

1. The effect of inhibiting the rate-limiting enzyme (3-hydroxy-3-methylglutaryl-CoA reductase, EC 1.1.1.88) in cholesterol synthesis on plasma lipid and lipoprotein concentrations was investigated in 16 patients with primary glomerular disease, heavy proteinuria, well-preserved renal function and hypercholesterolaemia. 2. Detailed studies of low-density lipoprotein metabolism were performed on eight patients before and after 12 weeks of simvastatin therapy. Radioiodinated tracers were used to quantify the fractional catabolic rate of low-density lipoprotein by apolipoprotein B/E receptors and alternative pathways. 3. Simvastatin produced consistent reductions in total plasma cholesterol concentration (median 36.9%), plasma low-density lipoprotein-cholesterol concentration (43.6%) and apolipoprotein B pool size (29.9%). 4. In contrast, the changes in kinetic parameters of low-density lipoprotein metabolism showed no clear pattern. Although an increase in the receptor-mediated catabolism of low-density lipoprotein was demonstrated in five patients, no change or a slight decrease was seen in three patients. Production rates were not significantly altered, although there was a slight decrease in the median value (from 12.4 to 9.7 mg day−1 kg−1). Plasma lathosterol concentration was reduced in all eight patients (range 34–71%), indirectly confirming significant inhibition of cholesterol synthesis. 5. These results suggest that, as in patients with primary moderate hyperlipidaemia, the significant cholesterol-lowering effect of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in the nephrotic syndrome is accompanied by variable changes in lipoprotein metabolism. The reasons for this heterogeneous response are unclear. This reflects our limited understanding of the metabolic basis of nephrotic hyperlipidaemia and the relationship between hepatic sterol synthesis and plasma lipoprotein kinetics.

Low density lipoprotein metabolism in rats with puromycin aminonucleoside-induced nephrotic syndrome

Metabolism ◽  
1989 ◽  
Vol 38 (5) ◽  
pp. 491-495 ◽  
Author(s):  
J. Joven ◽  
L. Masana ◽  
C. Villabona ◽  
E. Vilella ◽  
T. Bargalló ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Low Density ◽  
Puromycin Aminonucleoside

scholarly journals Modulation of hepatic apolipoprotein B, 3-hydroxy-3-methylglutaryl-CoA reductase and low-density lipoprotein receptor mRNA and plasma lipoprotein concentrations by defined dietary fats. Comparison of trimyristin, tripalmitin, tristearin and triolein

1995 ◽  
Vol 311 (1) ◽  
pp. 167-173 ◽  
Author(s):  
A J Bennett ◽  
M A Billett ◽  
A M Salter ◽  
E H Mangiapane ◽  
J S Bruce ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Plasma Lipids ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Dietary Fats ◽  
Low Density ◽  
Mrna Levels ◽  
Expression Of Genes ◽  
Coa Reductase

Different dietary fatty acids exert specific effects on plasma lipids but the mechanism by which this occurs is unknown. Hamsters were fed on low-cholesterol diets containing triacylglycerols enriched in specific saturated fatty acids, and effects on plasma lipids and the expression of genes involved in hepatic lipoprotein metabolism were measured. Trimyristin and tripalmitin caused significant rises in low-density lipoprotein (LDL) cholesterol which were accompanied by significant reductions in hepatic LDL receptor mRNA levels. Tripalmitin also increased hepatic expression of the apolipoprotein B gene, implying an increased production of LDL via very-low-density lipoprotein (VLDL) and decreased removal of LDL in animals fed this fat. Hepatic levels of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA did not vary significantly between the groups. Compared with triolein, tristearin had little effect on hepatic gene expression or total plasma cholesterol. However, it caused a marked decrease in VLDL cholesterol and a rise in LDL cholesterol such that overall it appeared to be neutral. Lipid analysis suggested a rapid desaturation of much of the dietary stearate. The differential changes in plasma lipids and hepatic mRNA levels induced by specific dietary fats suggests a role for fatty acids or a metabolite thereof in the regulation of the expression of genes involved in lipoprotein metabolism.

scholarly journals Lipoprotein Signatures of Cholesteryl Ester Transfer Protein and HMG-CoA Reductase Inhibition

2018 ◽  
Author(s):  
Johannes Kettunen ◽  
Michael V. Holmes ◽  
Elias Allara ◽  
Olga Anufrieva ◽  
Pauli Ohukainen ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Triglyceride Composition ◽  
Cholesterol Concentration ◽  
Resonance Spectroscopy ◽  
Low Density ◽  
Triglyceride Content ◽  
Cetp Inhibition

AbstractBackgroundCETP inhibition reduces vascular event rates but confusion surrounds its low-density lipoprotein (LDL)-cholesterol effects. We sought to clarify associations of genetic inhibition of CETP on detailed lipoproteins.Methods and ResultsWe used variants associated withCETP(rs247617) andHMGCR(rs12916) expression in 62,400 Europeans with detailed lipoprotein profiling from nuclear magnetic resonance spectroscopy. Genetic associations were scaled to 10% lower risk of coronary heart disease (CHD). Associations of lipoprotein measures with risk of incident CHD in three population-based cohorts (770 cases) were examined.CETPandHMGCRhad near-identical associations with LDL-cholesterol concentration estimated by Friedewald-equation.HMGCRhad a relatively consistent effect on cholesterol concentrations across all apolipoprotein B-containing lipoproteins.CETPhad stronger effects on remnant and very-low-density lipoprotein cholesterol but no effect on cholesterol concentrations in LDL defined by particle size (diameter 18–26 nm) (-0.02SD 95%CI: -0.10, 0.05 forCETPversus -0.24SD, 95%CI -0.30, -0.18 forHMGCR).CETPhad profound effects on lipid compositions of lipoproteins, with strong reductions in the triglyceride content of all highdensity lipoprotein (HDL) particles. These alterations in triglyceride composition within HDL subclasses were observationally associated with risk of CHD, independently of total cholesterol and triglycerides (strongest HR per 1-SD higher triglyceride composition in very-large HDL 1.35; 95%CI: 1.18, 1.54).ConclusionCETP inhibition does not affect size-specific LDL cholesterol but may lower CHD risk by lowering cholesterol in other apolipoprotein-B containing lipoproteins and lowering triglyceride content of HDL particles. Conventional composite lipid assays may mask heterogeneous effects of lipid-altering therapies.

scholarly journals Estrogen Deficiency after Menopause Does Not Result in Male Very-Low-Density Lipoprotein Metabolism Phenotype

2010 ◽  
Vol 95 (7) ◽  
pp. 3377-3384 ◽  
Author(s):  
Faidon Magkos ◽  
Elisa Fabbrini ◽  
B. Selma Mohammed ◽  
Bruce W. Patterson ◽  
Samuel Klein ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Premenopausal Women ◽  
Reproductive Hormones ◽  
Secretion Rate ◽  
Very Low Density Lipoprotein ◽  
Low Density

Context: Sex differences in lipid metabolism result in a less proatherogenic plasma lipid profile in premenopausal women than men. The mechanisms responsible for this are unclear but are thought to be related to differences in the sex hormone milieu in men and women. Objective: Our objective was to evaluate the effect of endogenous sex hormones on very-low-density lipoprotein (VLDL) triglyceride (TG) and apolipoprotein B-100 (apoB-100) metabolism. Experimental Design and Main Outcome Measures: We measured basal VLDL-TG and VLDL-apoB-100 concentrations and kinetics by using stable isotope-labeled tracers. Setting and Participants: Eight premenopausal women [age, 43 ± 8 yr; body mass index (BMI), 35 ± 4 kg/m2; mean ± sd], eight postmenopausal women (age, 55 ± 4 yr; BMI, 34 ± 4 kg/m2), and eight men (age, 41 ± 13 yr; BMI, 34 ± 4 kg/m2) were studied at Washington University School of Medicine, St. Louis, MO. Results: VLDL-TG secretion rate was approximately double (P < 0.05) in postmenopausal women and men compared with premenopausal women but not different in postmenopausal women and men. The secretion rate of VLDL-apoB-100 was not different in pre- and postmenopausal women but was greater (P < 0.05) in men than in women. Conclusions: Endogenous ovarian sex steroids are responsible for sexual dimorphism in VLDL-TG secretion, whereas VLDL-apoB-100 secretion is not regulated by female reproductive hormones.

Effect of Phenobarbitone on Plasma Apolipoprotein B and Plasma High-Density-Lipoprotein Cholesterol in Normal Subjects

1979 ◽  
Vol 56 (5) ◽  
pp. 501-504 ◽  
Author(s):  
P. N. Durrington
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Normal Subjects ◽  
Cholesterol Concentration ◽  
Low Density ◽  
Plasma High Density ◽  
Normal Men ◽  
Plasma Apolipoprotein

1. Further observations from an earlier study in which phenobarbitone in a dose of 180 mg daily was administered to ten normal men and women for 3 weeks are reported. There was a significant increase in plasma high-denity-lipoprotein (HDL) cholesterol concentration and in the concentration of both total plasma and low-density-lipoprotein (LDL) apolipoprotein B. 2. There was no change in the ratios of the cholesterol: apolipoprotein B and triglyceride: apolipoprotein B in LDL. 3. There was no significant change in plasma very-low-density-lipoprotein (VLDL) apolipoprotein B concentration and the proportion of lipid and apolipoprotein B in VLDL remained unchanged. 4. There was no change in the ratio of HDL:LDL cholesterol concentrations.

scholarly journals Effect of Low-Density Lipoprotein Apheresis on Kinetics of Apolipoprotein B in Heterozygous Familial Hypercholesterolemia1

2001 ◽  
Vol 86 (4) ◽  
pp. 1679-1686
Author(s):  
Cyrille Maugeais ◽  
Khadija Ouguerram ◽  
Regis Frénais ◽  
Pascale Maugère ◽  
Bernard Charbonnel ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Low Density ◽  
Fractional Catabolic Rate ◽  
Ldl Apheresis ◽  
Catabolic Rate ◽  
High Level

The acute reduction of low-density lipoprotein (LDL) cholesterol obtained by LDL-apheresis allows the role of the high level of circulating LDL on lipoprotein metabolism in heterozygous familial hypercholesterolemia (heterozygous FH) to be addressed. We studied apolipoprotein B (apoB) kinetics in five heterozygous FH patients before and the day after an apheresis treatment using endogenous labeling with [2H3]leucine. Compared with younger control subjects, heterozygous FH patients before apheresis showed a significant decrease in the fractional catabolic rate of LDL (0.24 ± 0.08 vs. 0.65 ± 0.22 day−1; P < 0.01), and LDL production was increased in heterozygous FH patients (18.9 ± 7.0 vs. 9.9 ± 4.2 mg/kg·day; P< 0.05). The modeling of postapheresis apoB kinetics was performed using a nonsteady state condition, taking into account the changing pool size of very low density lipoprotein (VLDL), intermediate density lipoprotein, and LDL apoB. The postapheresis kinetic parameters did not show statistical differences compared with preapheresis parameters in heterozygous FH patients; however, a trend for increases in fractional catabolic rate of LDL (0.24 ± 0.08 vs. 0.35± 0.09 day−1; P = 0.067) and the production of VLDL (13.7 ± 8.3 vs. 21.9 ± 1.6 mg/kg·day; P = 0.076) was observed. These results suggested that the marked decrease in plasma LDL obtained a short time after LDL-apheresis is able to stimulate LDL receptor activity and VLDL production in heterozygous FH.

Low-density lipoprotein metabolism in the nephrotic syndrome

Metabolism ◽  
1990 ◽  
Vol 39 (2) ◽  
pp. 187-192 ◽  
Author(s):  
Graham L. Warwick ◽  
Muriel J. Caslake ◽  
J.Michael Boulton-Jones ◽  
Morag Dagen ◽  
Christopher J. Packard ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Low Density
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