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- W3174404150 abstract "CETP inhibition has been used as a strategy to raise HDL cholesterol, but trials with two CETP inhibitors torcetrapib and dalcetrapib failed to prevent cardiovascular events for high-risk individuals. Of note, approximately 2/3 of patients in these clinical trials were obese. Obesity and fatty liver are known to significantly impact aspects of liver cholesterol metabolism and HDL biology. We propose that high-fat diet feeding (HFD) might adversely impact the effects of CETP inhibition on HDL composition and function. Mice naturally lack CETP expression, so we used CETP transgenic mice to evaluate the effects of administering the CETP inhibitor torcetrapib on HDL composition in chow- and HFD-fed CETP-transgenic mice. Because of the very short half-life of torcetrapib we used acute intravenous infusion of torcetrapib. In both diet groups torcetrapib infusion suppressed plasma CETP activity and raised HDL cholesterol content. In chow-fed CETP mice we found that torcetrapib resulted in changes in HDL composition that would be predicted to be favorable, including increases in apoA1, apoM and apoE protein levels for 2.5-fold ( P <0.01), 1.8-fold ( P <0.05) to 2-fold ( P <0.05), respectively. By contrast, in HFD-fed CETP mice those effects of torcetrapib were diminished, torcetrapib had no effect on apoA1, apoM or apoE. In addition, the acute phase protein SAA1 in HDL was increased significantly by torcetrapib only in HFD-fed mice. Our results show that the effect of pharmacologic CETP inhibition on HDL composition is context-specific to the diet. These findings may be helpful to understanding why CETP inhibition, while beneficial in early animal trials, failed to reduce cardiovascular events in clinical trials where most individuals were obese." @default.
- W3174404150 created "2021-07-05" @default.
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- W3174404150 date "2016-05-01" @default.
- W3174404150 modified "2023-09-24" @default.
- W3174404150 title "Abstract 237: Evaluating CETP Inhibition in Context: CETP Inhibition Modifies High-density Lipoprotein Composition in CETP-expressing Transgenic Mice Differently Depending on Diet" @default.
- W3174404150 doi "https://doi.org/10.1161/atvb.36.suppl_1.237" @default.
- W3174404150 hasPublicationYear "2016" @default.
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