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Influence of Simvastatin on apoB-100 Secretion in Non-Obese Subjects with Mild Hypercholesterolemia

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Lipids

Abstract

Statins decrease apoB-100-containing lipoproteins by increasing their fractional catabolic rates through LDL receptor-mediated uptake. Their influence on hepatic secretion of these lipoproteins is controversial. The objective of the study was to examine the influence of simvastatin on the secretion of apoB-100-containing lipoproteins in fasting non-obese subjects. Turnover of apoB-100-containing lipoproteins was investigated using stable isotope-labeled tracers. Multicompartmental modeling was used to derive kinetic parameters. Eight male subjects (BMI 25 ± 3 kg/m2) with mild hypercholesterolemia (LDL cholesterol 135 ± 30 mg/dL) and normal triglycerides (111 ± 44 mg/dL) were examined under no treatment (A), under chronic treatment with simvastatin 40 mg/day (B) and after an acute-on-chronic dosage of 80 mg simvastatin under chronic simvastatin treatment (C). Lipoprotein concentrations changed as expected under 40 mg/day simvastatin. Fractional catabolic rates increased in IDL and LDL but not in VLDL fractions versus control [VLDL +35% in B (n.s.) and +21% in C (n.s.); IDL +169% in B (P = 0.08) and +187% in C (P = 0.032); LDL +87% in B (P = 0.025) and +133% in C (P = 0.025)]. Chronic (B) and acute-on-chronic simvastatin treatment (C) did not affect lipoprotein production rates [VLDL −8 and −13%, IDL +47 and +38%, and LDL +19 and +30% in B and C, respectively (all comparisons n.s.)]. The data indicate that simvastatin does not influence the secretion of apoB-100-containing lipoproteins in non-obese subjects with near-normal LDL cholesterol concentrations.

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Abbreviations

apoB-100:

Apolipoprotein B-100

BMI:

Body mass index

CHOD-PAP:

Cholesterol oxidase phenol aminoantipyrine peroxidase

EDTA:

Ethylene-diamine-tetra-acetic acid

FCR:

Fractional catabolic rate

GPO-PAP:

Glycerol-3-phosphate oxidase phenol aminoantipyrine peroxidase

HDL:

High-density lipoproteins

HMG:

4-Hydroxy-3-methylglutaryl

IDL:

Intermediate-density lipoproteins

LDL:

Low-density lipoproteins

PR:

Production rate

VLDL:

Very low-density lipoproteins

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Acknowledgments

The authors wish to thank Mrs. Anja Kerksiek for her excellent technical assistance.

Conflict of interest statement

None.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, University of Bonn, Bonn, Germany

    Heiner K. Berthold, Jessica Mertens, Julia Birnbaum, Susanne Brämswig, Thomas Sudhop & Klaus von Bergmann

  2. Lipid Clinic, Interdisciplinary Metabolism Center, Charité University Medicine Berlin, Campus Virchow Clinic, Augustenburger Platz 1, 13353, Berlin, Germany

    Heiner K. Berthold

  3. School of Medicine and Pharmacology, University of Western Australia, Perth, Australia

    P. Hugh R. Barrett

  4. Department of Internal Medicine II, University of Cologne, Cologne, Germany

    Ioanna Gouni-Berthold

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  1. Heiner K. Berthold
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Correspondence to Heiner K. Berthold.

Additional information

H. K. Berthold and J. Mertens have contributed equally.

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Berthold, H.K., Mertens, J., Birnbaum, J. et al. Influence of Simvastatin on apoB-100 Secretion in Non-Obese Subjects with Mild Hypercholesterolemia. Lipids 45, 491–500 (2010). https://doi.org/10.1007/s11745-010-3420-5

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  • DOI: https://doi.org/10.1007/s11745-010-3420-5

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