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

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    4 Citations (Scopus)

    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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