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Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
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Different effects of compounds decreasing cholesteryl ester transfer protein activity on lipoprotein metabolism

Eric J Niesor1

  • 1Pharmaceuticals Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland. eric_j.niesor@roche.com

Current Opinion in Lipidology
|May 19, 2011
PubMed
Abstract

Insights

Pharmacological inhibition or modulation of cholesteryl ester transfer protein (CETP) affects lipoprotein profiles and HDL remodeling. Differences in CETP inhibition versus modulation are emerging, with ongoing studies to determine cardiovascular disease treatment relevance.

Area of Science:

  • Lipid metabolism
  • Cardiovascular pharmacology
  • Biochemistry

Background:

  • Cholesteryl ester transfer protein (CETP) facilitates lipid transfer between lipoproteins.
  • CETP activity influences HDL remodeling and reverse cholesterol transport.
  • Pharmacological targeting of CETP is a strategy for cardiovascular disease management.

Purpose of the Study:

  • To review the effects of decreasing CETP activity via pharmacological inhibition or modulation.
  • To compare these effects with human CETP deficiency.
  • To analyze impacts on lipoprotein characteristics, HDL remodeling, and function.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Analysis of data on CETP inhibitors (CETPi) and CETP modulators (CETPm).
  • Comparison of torcetrapib, anacetrapib, and dalcetrapib effects.

Main Results:

  • Torcetrapib, anacetrapib, and dalcetrapib inhibited cholesteryl ester transfer with varying potencies.
  • CETPi (torcetrapib, anacetrapib) inhibited homotypic HDL transfer; CETPm (dalcetrapib) did not.
  • Dalcatrapib uniquely increased fecal sterol excretion in a hamster model; clinical studies showed dose-dependent changes in lipoprotein composition.

Conclusions:

  • CETP inhibition and modulation yield distinct HDL remodeling and reverse cholesterol transport potentials.
  • Anacetrapib and dalcetrapib studies will clarify the clinical relevance of CETP inhibition versus modulation for cardiovascular disease treatment.

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