Title
Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin
Author
de Haan, W.
de Vries-van der Weij, J.
van der Hoorn, J.W.A.
Gautier, T.
van der Hoogt, C.C.
Westerterp, M.
Romijn, J.A.
Jukema, J.W.
Havekes, L.M.
Princen, H.M.G.
Rensen, P.C.N.
Publication year
2008
Abstract
BACKGROUND - Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even increased cardiovascular death in the recent Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events trial. Therefore, we evaluated the antiatherogenic potential and adverse effects of torcetrapib in humanized APOE*3-Leiden.CETP (E3L.CETP) mice. METHODS AND RESULTS - E3L.CETP mice were fed a cholesterol-rich diet without drugs or with torcetrapib (12 mg·kg·d), atorvastatin (2.8 mg·kg·d), or both for 14 weeks. Torcetrapib decreased CETP activity in both the absence and presence of atorvastatin (-74% and -73%, respectively; P
Subject
Biomedical Research
Atherosclerosis
Cholesteryl ester transfer proteins
Drugs
Lipids
Lipoproteins
Apolipoprotein E
Atorvastatin
Cholesterol
Cholesterol ester transfer protein
Collagen
High density lipoprotein cholesterol
Monocyte chemotactic protein 1
Torcetrapib
Atherosclerosis
Cholesterol blood level
Drug activity
Evaluation
Female
Inflammation
Macrophage
Monocyte
Mouse
Nonhuman
Phenotype
Sham feeding
Statistical significance
Animals
Atherosclerosis
Cholesterol Ester Transfer Proteins
Drug Synergism
Heptanoic Acids
Inflammation
Mice
Mice, Inbred Strains
Pyrroles
Quinolines
To reference this document use:
http://resolver.tudelft.nl/uuid:f64e6396-281a-4b2a-957f-f1ad702dbcaa
DOI
https://doi.org/10.1161/circulationaha.107.761965
TNO identifier
240771
ISSN
0009-7322
Source
Circulation, 117 (117), 2515-2522
Document type
article