QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.085522v1 315/1/363    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bach-Ngohou, K. Articles by Bard, J. M. Search for Related Content PubMed PubMed Citation Articles by Bach-Ngohou, K. Articles by Bard, J. M.

ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Influence of Atorvastatin on Apolipoprotein E and AI Kinetics in Patients with Type 2 Diabetes

Institut National de la Santé et de la Recherche Medicale U539, Centre de Recherche en Nutrition Humaine (K.B.-N., K.O., R.F., P.M., B.R.-P., Y.Z., M.K., J.M.B.), Laboratoire de Biochimie Spécialisée (K.B.-N.), and Clinique d'Endocrinologie, Maladies Métaboliques, Nutrition (Y.Z., M.K.), CHU Hôtel-Dieu, Nantes, France; and Laboratoire de Biochimie Fondamentale et Appliquée EA3823, UFR de Pharmacie, Nantes, France (B.R.-P., J.M.B.)

Atorvastatin reduces both plasma cholesterol and triglyceride concentrations in patients with type 2 diabetes, but mechanisms underlying triglyceride decrease and the effect of atorvastatin on high density lipoprotein (HDL) still remain unclear. Apolipoprotein (apo) E plays a crucial role in modulating production and clearance of triglyceride-rich very low density lipoprotein (VLDL). The main effect of apoAI is to modulate HDL metabolism. The aim of this work was to study the influence of atorvastatin on apoAI and apoE kinetics and to determine whether its hypocholesterolemic and hypotriglyceridemic effects could be related to changes in this apolipoprotein metabolism. Plasma VLDL-apoE, HDL-apoE, and HDL-apoAI were studied in seven patients with diabetes with mixed hyperlipidemia using a stable isotope labeling technique ([²H₃]leucine-primed constant infusion) and monocompartmental model before and after 2 months of treatment with 40 mg/day of atorvastatin. Plasma apoE concentration was significantly reduced (44.1 ± 19.1 versus 32 ± 11.6 mg/l, p < 0.05) after treatment. This decrease was associated with a diminution of HDL-apoE concentration (17.46 ± 6.71 versus 13.37 ± 6.05 mg/l, p < 0.05) and production rate (0.202 ± 0.085 versus 0.119 ± 0.047 mg/kg/day, p < 0.05), whereas an increase in VLDL-apoE concentration (6.44 ± 2.16 before versus 9.23 ± 4.02 mg/l after, p < 0.05) and production rate (0.827 ± 0.367 versus 1.524 ± 0.664 mg/kg/day, p < 0.05) was observed. No significant difference was observed after treatment for apoAI parameters. We conclude that atorvastatin treatment promotes different apoE distribution between HDL and VLDL, favoring VLDL apoE content. The increased number of apoE per VLDL particle suggests that atorvastatin could enhance the direct catabolism of triglyceride-rich VLDL through apoE receptor pathways.

Address correspondence to: Kalyane Bach, Laboratoire de Biochimie Spécialisée, CHU Hôtel-Dieu, 9 Quai Moncousu, 44093 Nantes Cedex 1, France. E-mail: kalyane.bach{at}chu-nantes.fr

This article has been cited by other articles:

				S. Lamon-Fava, M. R. Diffenderfer, P. H. R. Barrett, A. Buchsbaum, N. R. Matthan, A. H. Lichtenstein, G. G. Dolnikowski, K. Horvath, B. F. Asztalos, V. Zago, et al. Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism J. Lipid Res., August 1, 2007; 48(8): 1746 - 1753. [Abstract] [Full Text] [PDF]

				R. Ramakrishnan Studying apolipoprotein turnover with stable isotope tracers: correct analysis is by modeling enrichments J. Lipid Res., December 1, 2006; 47(12): 2738 - 2753. [Abstract] [Full Text] [PDF]

				S. Rashid, B. W. Patterson, and G. F. Lewis Thematic review series: Patient-Oriented Research. What have we learned about HDL metabolism from kinetics studies in humans? J. Lipid Res., August 1, 2006; 47(8): 1631 - 1642. [Abstract] [Full Text] [PDF]

				D. C Chan, G. F Watts, M. N Nguyen, and P H. R Barrett Factorial study of the effect of n-3 fatty acid supplementation and atorvastatin on the kinetics of HDL apolipoproteins A-I and A-II in men with abdominal obesity Am. J. Clinical Nutrition, July 1, 2006; 84(1): 37 - 43. [Abstract] [Full Text] [PDF]