Altered apolipoprotein B metabolism in very low density lipoprotein from lovastatin-treated guinea pigs

Lars Berglund, W. F. Beltz, R. L. Elam, J. L. Witztum

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Previous studies have shown that treatment of guinea pigs with lovastatin alters the composition and the metabolic properties of circulating low density lipoprotein (LDL). Specifically, LDL isolated from lovastatin- treated animals is cleared from plasma more slowly than LDL isolated from control animals, when injected into the guinea pig. In the present study, we examine whether lovastatin also affects the metabolic properties of very low density lipoprotein (VLDL), the metabolic precursor of LDL. VLDL isolated from lovastatin-treated guinea pigs (L-VLDL) and VLDL isolated from untreated (control) guinea pigs (C-VLDL) were radioiodinated and simultaneously injected into eight untreated guinea pigs. Radioactivity associated with apolipoprotein B-100 (apoB) was measured in four plasma density fractions and analyzed using a compartmental model consisting of fast and slow pools for VLDL, fast and slow pools for intermediate density lipoprotein (IDL), and a single slow pool for LDL. The fractional catabolic rate (FCR) for C-VLDL apoB was 2.8 ± 1.0 h-1 and for L-VLDL apoB was 5.1 ± 2.0 h-1 (P < 0.002, paired t test). The fractions of control and lovastatin VLDL apoB converted to LDL averaged 0.15 ± 0.15 and 0.02 ± 0.02, respectively (P < 0.05, paired t test). Finally, the FCRs of LDL apoB derived from control and lovastatin VLDL were similar (0.059 ± 0.007 h-1 and 0.083 ± 0.038 h-1, respectively; paired t test not significant). These data indicate that L- VLDL was irreversibly removed from the plasma of an untreated guinea pig more rapidly than was C-VLDL. Thus, the metabolic behavior of VLDL apoB is affected by lovastatin. Therefore, changes in lipoprotein particles themselves must be considered in assessing the overall impact of treatment with lovastatin.

Original languageEnglish (US)
Pages (from-to)956-965
Number of pages10
JournalJournal of Lipid Research
Volume35
Issue number6
StatePublished - 1994

Fingerprint

Lovastatin
VLDL Lipoproteins
Apolipoproteins B
Metabolism
Guinea Pigs
Apolipoprotein B-100
LDL Lipoproteins
Animals
IDL Lipoproteins
Plasmas
Plasma density
Radioactivity
Lipoproteins

Keywords

  • lipoprotein heterogeneity
  • low density lipoprotein
  • multicompartmental modeling
  • SAAM

ASJC Scopus subject areas

  • Endocrinology

Cite this

Altered apolipoprotein B metabolism in very low density lipoprotein from lovastatin-treated guinea pigs. / Berglund, Lars; Beltz, W. F.; Elam, R. L.; Witztum, J. L.

In: Journal of Lipid Research, Vol. 35, No. 6, 1994, p. 956-965.

Research output: Contribution to journalArticle

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abstract = "Previous studies have shown that treatment of guinea pigs with lovastatin alters the composition and the metabolic properties of circulating low density lipoprotein (LDL). Specifically, LDL isolated from lovastatin- treated animals is cleared from plasma more slowly than LDL isolated from control animals, when injected into the guinea pig. In the present study, we examine whether lovastatin also affects the metabolic properties of very low density lipoprotein (VLDL), the metabolic precursor of LDL. VLDL isolated from lovastatin-treated guinea pigs (L-VLDL) and VLDL isolated from untreated (control) guinea pigs (C-VLDL) were radioiodinated and simultaneously injected into eight untreated guinea pigs. Radioactivity associated with apolipoprotein B-100 (apoB) was measured in four plasma density fractions and analyzed using a compartmental model consisting of fast and slow pools for VLDL, fast and slow pools for intermediate density lipoprotein (IDL), and a single slow pool for LDL. The fractional catabolic rate (FCR) for C-VLDL apoB was 2.8 ± 1.0 h-1 and for L-VLDL apoB was 5.1 ± 2.0 h-1 (P < 0.002, paired t test). The fractions of control and lovastatin VLDL apoB converted to LDL averaged 0.15 ± 0.15 and 0.02 ± 0.02, respectively (P < 0.05, paired t test). Finally, the FCRs of LDL apoB derived from control and lovastatin VLDL were similar (0.059 ± 0.007 h-1 and 0.083 ± 0.038 h-1, respectively; paired t test not significant). These data indicate that L- VLDL was irreversibly removed from the plasma of an untreated guinea pig more rapidly than was C-VLDL. Thus, the metabolic behavior of VLDL apoB is affected by lovastatin. Therefore, changes in lipoprotein particles themselves must be considered in assessing the overall impact of treatment with lovastatin.",
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