title: Influence of simvastatin on apoB-100 secretion in non-obese subjects with mild hypercholesterolemia.
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/m(2)) 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.
authors.affiliation: Department of Clinical Pharmacology, University of Bonn, Bonn, Germany. heiner.berthold@charite.de
authors.forename: Heiner K
authors.initials: HK
authors.lastname: Berthold
authors.forename: Jessica
authors.initials: J
authors.lastname: Mertens
authors.forename: Julia
authors.initials: J
authors.lastname: Birnbaum
authors.forename: Susanne
authors.initials: S
authors.lastname: Brämswig
authors.forename: Thomas
authors.initials: T
authors.lastname: Sudhop
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
authors.forename: Klaus
authors.initials: K
authors.lastname: von Bergmann
authors.forename: Ioanna
authors.initials: I
authors.lastname: Gouni-Berthold
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D053299:Apolipoprotein B-100 / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D018592:Cross-Over Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D008078:Cholesterol, LDL; D019821:Simvastatin
references.citation: Arterioscler Thromb Vasc Biol. 1999 Dec;19(12):2966-74
references.pmid: 10591677
references.citation: Arterioscler Thromb Vasc Biol. 1997 Oct;17(10):1910-7
references.pmid: 9351353
references.citation: J Lipid Res. 1996 Mar;37(3):439-47
references.pmid: 8728309
references.citation: Arterioscler Thromb. 1993 Feb;13(2):170-89
references.pmid: 8427854
references.citation: Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8091-5
references.pmid: 11607211
references.citation: J Pharmacol Exp Ther. 2003 Jul;306(1):332-7
references.pmid: 12684543
references.citation: J Intern Med. 1990 Feb;227(2):81-94
references.pmid: 2105373
references.citation: Proc Natl Acad Sci U S A. 1983 Jul;80(13):4124-8
references.pmid: 6575399
references.citation: Metabolism. 2000 Sep;49(9):1204-10
references.pmid: 11016905
references.citation: J Lipid Res. 2007 Aug;48(8):1746-53
references.pmid: 17526934
references.citation: J Lipid Res. 1990 Apr;31(4):567-82
references.pmid: 2351867
references.citation: Curr Opin Lipidol. 1996 Jun;7(3):132-8
references.pmid: 8818509
references.citation: Biochem J. 1989 Mar 15;258(3):807-16
references.pmid: 2730568
references.citation: J Clin Invest. 1987 Dec;80(6):1692-7
references.pmid: 3680522
references.citation: J Clin Endocrinol Metab. 2002 May;87(5):2283-9
references.pmid: 11994377
references.citation: J Lipid Res. 2005 Dec;46(12):2735-44
references.pmid: 16162940
references.citation: J Lipid Res. 1997 Oct;38(10):2071-8
references.pmid: 9374129
references.citation: J Lipid Res. 1993 Feb;34(2):167-79
references.pmid: 8381452
references.citation: J Lipid Res. 2007 May;48(5):1204-11
references.pmid: 17325388
references.citation: Clin Sci (Lond). 1995 Feb;88(2):225-33
references.pmid: 7720348
references.citation: Biochim Biophys Acta. 1990 Jun 14;1044(3):297-304
references.pmid: 2364096
references.citation: N Engl J Med. 1996 Oct 3;335(14):1001-9
references.pmid: 8801446
references.citation: Atherosclerosis. 1988 Mar;70(1-2):131-43
references.pmid: 3162680
references.citation: Clin Investig. 1993 Nov;71(11):939-46
references.pmid: 8312689
references.citation: Arterioscler Thromb. 1993 May;13(5):629-36
references.pmid: 8485114
references.citation: Atherosclerosis. 1989 Dec;80(2):101-9
references.pmid: 2610723
references.citation: Metabolism. 1995 Apr;44(4):466-73
references.pmid: 7723669
references.citation: Diabetologia. 1995 Aug;38(8):959-67
references.pmid: 7589883
references.citation: J Lipid Res. 1970 Nov;11(6):583-95
references.pmid: 4100998
references.citation: J Lipid Res. 1985 Dec;26(12):1464-75
references.pmid: 3853581
references.citation: Am J Cardiol. 2004 Feb 15;93(4):414-20
references.pmid: 14969613
references.citation: N Engl J Med. 1995 Nov 16;333(20):1301-7
references.pmid: 7566020
references.citation: J Lipid Res. 1983 Sep;24(9):1261-7
references.pmid: 6631250
references.citation: Eur J Clin Invest. 2000 Aug;30(8):685-94
references.pmid: 10964160
references.citation: Am J Cardiol. 2004 Jan 1;93(1):31-9
references.pmid: 14697462
references.citation: Eur J Clin Invest. 1995 Aug;25(8):559-67
references.pmid: 7589011