Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism.
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 apoB PR regulation.
Lamon-Fava
Stefania
S
Lipid Metabolism Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. stefania.lamon-fava@tufts.edu
Diffenderfer
Margaret R
MR
Barrett
P Hugh R
PH
Buchsbaum
Aaron
A
Matthan
Nirupa R
NR
Lichtenstein
Alice H
AH
Dolnikowski
Gregory G
GG
Horvath
Katalin
K
Asztalos
Bela F
BF
Zago
Valeria
V
Schaefer
Ernst J
EJ
D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000097:blood*; D053299:Apolipoprotein B-100 / Q000097:blood*; D053283:Apolipoprotein B-48 / Q000097:blood*; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin