Related Experiment Video
Updated: Mar 2, 2026
Production of Apolipoprotein C-III Knockout Rabbits using Zinc Finger Nucleases
Published on: November 18, 2013
Dalcetrapib and anacetrapib differently impact HDL structure and function in rabbits and monkeys
Mathieu R Brodeur1, David Rhainds1, Daniel Charpentier1
1Montreal Heart Institute, Montreal, Quebec, Canada.
Insights
Cholesteryl ester transfer protein inhibitors (CETPis) alter high-density lipoprotein (HDL) levels and function. Species-specific responses to dalcetrapib highlight variations in HDL metabolism and cholesterol efflux capacity.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Lipid Metabolism
Background:
- Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol (HDL-C).
- The impact of CETP inhibition on HDL structure and function in species with high CETP levels is not well understood.
- Dalcetrapib and anacetrapib are CETP inhibitors (CETPis) in clinical trials.
Purpose of the Study:
- To investigate the effects of dalcetrapib and anacetrapib on HDL particle subclass distribution and cholesterol efflux capacity.
- To compare the effects of these CETPis in rabbits and monkeys.
Main Methods:
- New Zealand White rabbits and vervet monkeys were treated with dalcetrapib and anacetrapib.
- HDL particle subclass distribution and cholesterol efflux capacity were measured.
- Changes in HDL-C and LDL-C levels were analyzed.
Main Results:
- In rabbits, CETPis increased HDL-C, altered HDL subclasses (α-migrating HDL), and enhanced ABCA1-induced cholesterol efflux.
- In vervet monkeys, anacetrapib showed similar effects to rabbits.
- Dalcetrapib in vervet monkeys paradoxically increased LDL-C and decreased HDL-C, reduced α- and preβ-HDL levels, and decreased cholesterol efflux capacity.
Conclusions:
- CETP inhibitors modulate plasma levels of mature and small HDL in vivo, affecting cholesterol efflux capacity.
- Dalcetrapib's opposing effects in different species suggest its impact on HDL metabolism is highly dependent on the metabolic environment.
Abstract:
Inhibition of cholesteryl ester transfer protein (CETP) increases HDL cholesterol (HDL-C) levels. However, the circulating CETP level varies and the impact of its inhibition in species with high CETP levels on HDL structure and function remains poorly characterized. This study investigated the effects of dalcetrapib and anacetrapib, the two CETP inhibitors (CETPis) currently being tested in large clinical outcome trials, on HDL particle subclass distribution and cholesterol efflux capacity of serum in rabbits and monkeys. New Zealand White rabbits and vervet monkeys received dalcetrapib and anacetrapib. In rabbits, CETPis increased HDL-C, raised small and large α-migrating HDL, and increased ABCA1-induced cholesterol efflux. In vervet monkeys, although anacetrapib produced similar results, dalcetrapib caused opposite effects because the LDL-C level was increased by 42% and HDL-C decreased by 48% (P < 0.01). The levels of α- and preβ-HDL were reduced by 16% (P < 0.001) and 69% (P < 0.01), resulting in a decrease of the serum cholesterol efflux capacity. CETPis modulate the plasma levels of mature and small HDL in vivo and consequently the cholesterol efflux capacity. The opposite effects of dalcetrapib in different species indicate that its impact on HDL metabolism could vary greatly according to the metabolic environment.
Related Concept Videos
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:29Pharmacogenomics: Identification of New Drug Targets