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), intermedi...
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| Veröffentlicht in: | Journal of lipid research Jg. 48; H. 8; S. 1746 - 1753 |
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| Format: | Journal Article |
| Sprache: | Englisch |
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Elsevier
01.08.2007
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| ISSN: | 0022-2275 |
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| Abstract | 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. |
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| AbstractList | 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. 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.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. |
| Author | Diffenderfer, Margaret R Barrett, P Hugh R Schaefer, Ernst J Dolnikowski, Gregory G Asztalos, Bela F Lichtenstein, Alice H Zago, Valeria Matthan, Nirupa R Horvath, Katalin Lamon-Fava, Stefania Buchsbaum, Aaron |
| Author_xml | – sequence: 1 givenname: Stefania surname: Lamon-Fava fullname: Lamon-Fava, Stefania email: stefania.lamon-fava@tufts.edu organization: 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 – sequence: 2 givenname: Margaret R surname: Diffenderfer fullname: Diffenderfer, Margaret R – sequence: 3 givenname: P Hugh R surname: Barrett fullname: Barrett, P Hugh R – sequence: 4 givenname: Aaron surname: Buchsbaum fullname: Buchsbaum, Aaron – sequence: 5 givenname: Nirupa R surname: Matthan fullname: Matthan, Nirupa R – sequence: 6 givenname: Alice H surname: Lichtenstein fullname: Lichtenstein, Alice H – sequence: 7 givenname: Gregory G surname: Dolnikowski fullname: Dolnikowski, Gregory G – sequence: 8 givenname: Katalin surname: Horvath fullname: Horvath, Katalin – sequence: 9 givenname: Bela F surname: Asztalos fullname: Asztalos, Bela F – sequence: 10 givenname: Valeria surname: Zago fullname: Zago, Valeria – sequence: 11 givenname: Ernst J surname: Schaefer fullname: Schaefer, Ernst J |
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| SubjectTerms | Anticholesteremic Agents - administration & dosage Anticholesteremic Agents - pharmacology Apolipoprotein A-I - blood Apolipoprotein B-100 - blood Apolipoprotein B-48 - blood Atorvastatin campesterol Cholesterol - blood Cholesterol - metabolism Cholesterol, LDL - blood Cholesterol, LDL - metabolism Cross-Over Studies Dose-Response Relationship, Drug Female Heptanoic Acids - administration & dosage Heptanoic Acids - pharmacology Humans Kinetics lathosterol Male Middle Aged Pyrroles - administration & dosage Pyrroles - pharmacology Time Factors Triglycerides - blood Triglycerides - metabolism |
| Title | Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism |
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