Received for publication March 24, 2005.
Revised July 8, 2005.
Accepted for publication July 8, 2005.

Influence of atorvastatin on apolipoprotein E and AI kinetics in type 2 diabetes patients

Abstract

Background and aims: Atorvastatin reduces both plasma cholesterol and triglyceride concentrations in type 2 diabetic patients, but mechanisms underlying triglyceride decrease and the effect of atorvastatin on 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 if its hypocholesterolemic and hypotriglyceridemic effects could be related to changes in these apolipoprotein metabolism. Methods: Plasma VLDL-apoE, HDL-apoE and -apoAI were studied in 7 diabetics with mixed hyperlipidemia using stable-isotope labelling technique ([2H3]-leucine primed-constant infusion) and monocompartmental model, before and after 2 months of treatment with 40 mg.d-1 atorvastatin. Results: Plasma apoE concentration was significantly reduced (44.1±19.1 vs 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 vs 13.37±6.05 mg/l, p<0.05) and production rate (0.202±0.085 vs 0.119±0.047 mg/Kg/d, p<0.05), while an increase in VLDL-apoE concentration (6.44±2.16 before vs 9.23±4.02 mg/l after, p<0.05) and production rate (0.827±0.367 vs 1.524±0.664 mg/Kg/d, p<0.05) was observed. No significant difference was observed after treatment for apoAI parameters. Conclusion: We conclude that atorvastatin treatment promotes different apoE distribution between HDL and VLDL, favouring 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.

Key words: apolipoprotein AI, apolipoprotein E, atorvastatin, kinetic studies, mixed dyslipidemia, type 2 diabetes

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