出版社：American Society for Biochemistry and Molecular Biology
摘要：Nine hypercholesterolemic and hypertriglyceridemic subjectswere enrolled in a randomized, placebo-controlled, double-blind,crossover study to test the effect of atorvastatin 20 mg/dayand 80 mg/day on the kinetics of apolipoprotein B-100 (apoB-100)in triglyceride-rich lipoprotein (TRL), intermediate densitylipoprotein (IDL), and LDL, of apoB-48 in TRL, and of apoA-Iin HDL. Compared with placebo, atorvastatin 20 mg/day was associatedwith significant reductions in TRL, IDL, and LDL apoB-100 poolsize as a result of significant increases in fractional catabolicrate (FCR) without changes in production rate (PR). Comparedwith the 20 mg/day dose, atorvastatin 80 mg/day caused a furthersignificant reduction in the LDL apoB-100 pool size as a resultof a further increase in FCR. ApoB-48 pool size was reducedsignificantly by both atorvastatin doses, and this reductionwas associated with nonsignificant increases in FCR. The lathosterol-campesterolratio was decreased by atorvastatin treatment, and changes inthis ratio were inversely correlated with changes in TRL apoB-100and apoB-48 PR. No significant effect on apoA-I kinetics wasobserved at either dose of atorvastatin. Our data indicate thatatorvastatin reduces apoB-100- and apoB-48-containing lipoproteinsby increasing their catabolism and has a dose-dependent effecton LDL apoB-100 kinetics. Atorvastatin-mediated changes in cholesterolhomeostasis may contribute to apoB PR regulation.Supplementary key words kinetics • lathosterol • campesterol
