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Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice

Willeke de Haan1, Caroline C van der Hoogt, Marit Westerterp

  • 1Netherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands. W.de_Haan.ENDO@lumc.nl

Atherosclerosis
|September 18, 2007
PubMed

Insights

Statins increase high-density lipoprotein (HDL)-cholesterol by reducing cholesteryl ester transfer protein (CETP) activity. This study shows atorvastatin boosts HDL in mice by downregulating CETP expression, lowering cholesterol transfer to very-low-density lipoprotein (VLDL).

Area of Science:

  • Cardiovascular Science
  • Lipid Metabolism

Background:

  • Statins lower LDL-cholesterol and modestly increase HDL-cholesterol.
  • Statins also decrease cholesteryl ester transfer protein (CETP) mass and activity.
  • The role of CETP expression in statin-induced HDL-cholesterol increase is unclear.

Purpose of the Study:

  • To determine if the HDL-increasing effect of statins depends on CETP expression.
  • To investigate the impact of atorvastatin on CETP expression and activity.

Main Methods:

  • APOE*3-Leiden (E3L) mice were crossbred with mice expressing human CETP to create E3L.CETP mice.
  • Mice were fed a Western-type diet with or without atorvastatin.
  • Plasma cholesterol, HDL-cholesterol, hepatic gene expression, CETP expression, and CETP activity were measured.

Main Results:

  • Atorvastatin reduced plasma cholesterol in both E3L and E3L.CETP mice.
  • HDL-cholesterol increased significantly only in E3L.CETP mice treated with atorvastatin (+52%).
  • Atorvastatin down-regulated hepatic CETP mRNA expression, plasma CETP levels, and CETP activity in E3L.CETP mice.

Conclusions:

  • Atorvastatin increases HDL-cholesterol in E3L.CETP mice.
  • This increase is mediated by reduced CETP-dependent cholesterol transfer from HDL to VLDL.
  • Lower hepatic CETP expression and a reduced VLDL pool contribute to the observed HDL elevation.
Abstract

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