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

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 ani...

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Main Authors: L F Berglund, W F Beltz, R L Elam, J L Witztum
Format: Article
Language:English
Published: Elsevier 1994-06-01
Series:Journal of Lipid Research
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520401105
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author L F Berglund
W F Beltz
R L Elam
J L Witztum
author_facet L F Berglund
W F Beltz
R L Elam
J L Witztum
author_sort L F Berglund
collection DOAJ
description 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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spelling doaj.art-91eda47e31d94e64a44a6f606dfb70f02022-12-21T21:56:34ZengElsevierJournal of Lipid Research0022-22751994-06-01356956965Altered apolipoprotein B metabolism in very low density lipoprotein from lovastatin-treated guinea pigs.L F Berglund0W F Beltz1R L Elam2J L Witztum3Department of Medicine, University of California, San Diego, La Jolla 92093-0682.Department of Medicine, University of California, San Diego, La Jolla 92093-0682.Department of Medicine, University of California, San Diego, La Jolla 92093-0682.Department of Medicine, University of California, San Diego, La Jolla 92093-0682.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.http://www.sciencedirect.com/science/article/pii/S0022227520401105
spellingShingle L F Berglund
W F Beltz
R L Elam
J L Witztum
Altered apolipoprotein B metabolism in very low density lipoprotein from lovastatin-treated guinea pigs.
Journal of Lipid Research
title Altered apolipoprotein B metabolism in very low density lipoprotein from lovastatin-treated guinea pigs.
title_full Altered apolipoprotein B metabolism in very low density lipoprotein from lovastatin-treated guinea pigs.
title_fullStr Altered apolipoprotein B metabolism in very low density lipoprotein from lovastatin-treated guinea pigs.
title_full_unstemmed Altered apolipoprotein B metabolism in very low density lipoprotein from lovastatin-treated guinea pigs.
title_short Altered apolipoprotein B metabolism in very low density lipoprotein from lovastatin-treated guinea pigs.
title_sort altered apolipoprotein b metabolism in very low density lipoprotein from lovastatin treated guinea pigs
url http://www.sciencedirect.com/science/article/pii/S0022227520401105
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AT rlelam alteredapolipoproteinbmetabolisminverylowdensitylipoproteinfromlovastatintreatedguineapigs
AT jlwitztum alteredapolipoproteinbmetabolisminverylowdensitylipoproteinfromlovastatintreatedguineapigs