Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48 and A-I metabolism

S. Lamon-Fava, M.R. Diffenderfer, Hugh Barrett, A. Buchsbaum, N.R. Matthan, A.H. Lichtenstein, G.G. Dolnikowski, K. Horvath, B.F. Asztalos, V. Zago, E.J. Schaefer

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    Nine hypercholesterolemic and hypertriglyceridemic subjects were enrolled in a randomized, placebo-controlled, double-blind, crossover study to test the effect of atorvastatin 20 mg/day and 80 mg/day on the kinetics of apolipoprotein B-100 ( apoB-100) in triglyceride-rich lipoprotein (TRL), intermediate density lipoprotein ( IDL), and LDL, of apoB-48 in TRL, and of apoA-I in HDL. Compared with placebo, atorvastatin 20 mg/day was associated with significant reductions in TRL, IDL, and LDL apoB-100 pool size as a result of significant increases in fractional catabolic rate ( FCR) without changes in production rate ( PR). Compared with the 20 mg/day dose, atorvastatin 80 mg/day caused a further significant reduction in the LDL apoB-100 pool size as a result of a further increase in FCR. ApoB-48 pool size was reduced significantly by both atorvastatin doses, and this reduction was associated with nonsignificant increases in FCR. The lathosterol-campesterol ratio was decreased by atorvastatin treatment, and changes in this ratio were inversely correlated with changes in TRL apoB-100 and apoB-48 PR. No significant effect on apoA-I kinetics was observed at either dose of atorvastatin. Our data indicate that atorvastatin reduces apoB-100- and apoB-48- containing lipoproteins by increasing their catabolism and has a dose-dependent effect on LDL apoB-100 kinetics. Atorvastatin-mediated changes in cholesterol homeostasis may contribute to apo-BPR regulation.
    Original languageEnglish
    Pages (from-to)1746-1753
    JournalJournal of Lipid Research
    Issue number8
    Publication statusPublished - 2007


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