Rosuvastatin enhances the catabolism of LDL apoB-100 in subjects with combined hyperlipidemia in a dose dependent manner

N.A. Le, M.R. Diffenderfer, N. Thongtang, Esther Ooi, Hugh Barrett, K.V. Horvath, G.G. Dolnikowski, B.F. Asztalos, E.J. Schaefer, W.V. Brown

    Research output: Contribution to journalArticle

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    Abstract

    © 2015 AOCS. Dose-associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B-100 in triacylglycerol rich lipoprotein (TRL, d <1.019 g/ml) and low density lipoprotein (LDL) and of apoA-I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB-100 production rate (PR), as well as increase apoB-100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB-100 in TRL and LDL and apoA-I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography-mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54 % (both P <0.0001), triacylglycerol by 14 % (ns) and 35 % (P <0.01), apoB by 30 and 36 % (both P <0.0001), respectively, and had no significant effects on HDL cholesterol or apoA-I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB-100 FCR by 36 and 46 % (both ns) and LDL apoB-100 by 63 and 102 % (both P <0.05), respectively. HDL apoA-I PR increased with low dose rosuvastatin (12 %, P <0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB-100 PR or HDL apoA-I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB-100, with no significant effects on apoB-100 production or HDL apoA-I kinetics.
    Original languageEnglish
    Pages (from-to)447-458
    JournalLipids
    Volume50
    Issue number5
    DOIs
    Publication statusPublished - 2015

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    Apolipoprotein B-100
    Hyperlipidemias
    LDL Lipoproteins
    Apolipoprotein A-I
    HDL Lipoproteins
    Triglycerides
    Cholesterol
    Rosuvastatin Calcium
    Kinetics
    Apolipoproteins B
    Metabolism
    Isotopes
    Gas chromatography
    LDL Cholesterol
    Gas Chromatography-Mass Spectrometry
    HDL Cholesterol
    Lipoproteins
    Mass spectrometry
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    Cite this

    Le, N.A. ; Diffenderfer, M.R. ; Thongtang, N. ; Ooi, Esther ; Barrett, Hugh ; Horvath, K.V. ; Dolnikowski, G.G. ; Asztalos, B.F. ; Schaefer, E.J. ; Brown, W.V. / Rosuvastatin enhances the catabolism of LDL apoB-100 in subjects with combined hyperlipidemia in a dose dependent manner. In: Lipids. 2015 ; Vol. 50, No. 5. pp. 447-458.
    @article{aebc8a8dac2a4c9c89918fb11ea81c34,
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    abstract = "{\circledC} 2015 AOCS. Dose-associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B-100 in triacylglycerol rich lipoprotein (TRL, d <1.019 g/ml) and low density lipoprotein (LDL) and of apoA-I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB-100 production rate (PR), as well as increase apoB-100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB-100 in TRL and LDL and apoA-I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography-mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54 {\%} (both P <0.0001), triacylglycerol by 14 {\%} (ns) and 35 {\%} (P <0.01), apoB by 30 and 36 {\%} (both P <0.0001), respectively, and had no significant effects on HDL cholesterol or apoA-I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB-100 FCR by 36 and 46 {\%} (both ns) and LDL apoB-100 by 63 and 102 {\%} (both P <0.05), respectively. HDL apoA-I PR increased with low dose rosuvastatin (12 {\%}, P <0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB-100 PR or HDL apoA-I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB-100, with no significant effects on apoB-100 production or HDL apoA-I kinetics.",
    author = "N.A. Le and M.R. Diffenderfer and N. Thongtang and Esther Ooi and Hugh Barrett and K.V. Horvath and G.G. Dolnikowski and B.F. Asztalos and E.J. Schaefer and W.V. Brown",
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    pages = "447--458",
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    Le, NA, Diffenderfer, MR, Thongtang, N, Ooi, E, Barrett, H, Horvath, KV, Dolnikowski, GG, Asztalos, BF, Schaefer, EJ & Brown, WV 2015, 'Rosuvastatin enhances the catabolism of LDL apoB-100 in subjects with combined hyperlipidemia in a dose dependent manner' Lipids, vol. 50, no. 5, pp. 447-458. https://doi.org/10.1007/s11745-015-4005-0

    Rosuvastatin enhances the catabolism of LDL apoB-100 in subjects with combined hyperlipidemia in a dose dependent manner. / Le, N.A.; Diffenderfer, M.R.; Thongtang, N.; Ooi, Esther; Barrett, Hugh; Horvath, K.V.; Dolnikowski, G.G.; Asztalos, B.F.; Schaefer, E.J.; Brown, W.V.

    In: Lipids, Vol. 50, No. 5, 2015, p. 447-458.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Rosuvastatin enhances the catabolism of LDL apoB-100 in subjects with combined hyperlipidemia in a dose dependent manner

    AU - Le, N.A.

    AU - Diffenderfer, M.R.

    AU - Thongtang, N.

    AU - Ooi, Esther

    AU - Barrett, Hugh

    AU - Horvath, K.V.

    AU - Dolnikowski, G.G.

    AU - Asztalos, B.F.

    AU - Schaefer, E.J.

    AU - Brown, W.V.

    PY - 2015

    Y1 - 2015

    N2 - © 2015 AOCS. Dose-associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B-100 in triacylglycerol rich lipoprotein (TRL, d <1.019 g/ml) and low density lipoprotein (LDL) and of apoA-I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB-100 production rate (PR), as well as increase apoB-100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB-100 in TRL and LDL and apoA-I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography-mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54 % (both P <0.0001), triacylglycerol by 14 % (ns) and 35 % (P <0.01), apoB by 30 and 36 % (both P <0.0001), respectively, and had no significant effects on HDL cholesterol or apoA-I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB-100 FCR by 36 and 46 % (both ns) and LDL apoB-100 by 63 and 102 % (both P <0.05), respectively. HDL apoA-I PR increased with low dose rosuvastatin (12 %, P <0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB-100 PR or HDL apoA-I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB-100, with no significant effects on apoB-100 production or HDL apoA-I kinetics.

    AB - © 2015 AOCS. Dose-associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B-100 in triacylglycerol rich lipoprotein (TRL, d <1.019 g/ml) and low density lipoprotein (LDL) and of apoA-I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB-100 production rate (PR), as well as increase apoB-100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB-100 in TRL and LDL and apoA-I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography-mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54 % (both P <0.0001), triacylglycerol by 14 % (ns) and 35 % (P <0.01), apoB by 30 and 36 % (both P <0.0001), respectively, and had no significant effects on HDL cholesterol or apoA-I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB-100 FCR by 36 and 46 % (both ns) and LDL apoB-100 by 63 and 102 % (both P <0.05), respectively. HDL apoA-I PR increased with low dose rosuvastatin (12 %, P <0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB-100 PR or HDL apoA-I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB-100, with no significant effects on apoB-100 production or HDL apoA-I kinetics.

    U2 - 10.1007/s11745-015-4005-0

    DO - 10.1007/s11745-015-4005-0

    M3 - Article

    VL - 50

    SP - 447

    EP - 458

    JO - Lipids

    JF - Lipids

    SN - 0024-4201

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    ER -