Journal
AMERICAN JOURNAL OF CARDIOLOGY
Volume 104, Issue 10A, Pages 39E-45EPublisher
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
DOI: 10.1016/j.amjcard.2009.09.018
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- Merck Co., Inc.
- Roche Pharmaceuticals
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Cholesterol ester transfer protein (CETP) deficiency or inhibition results in dramatic elevations of high-density lipoprotein (HDL) levels, but there has been concern that HDL might be dysfunctional in its ability to promote efflux of cholesterol from macrophage foam cells or to mediate reverse cholesterol transport. Using cholesterol-loaded cultured macrophages, HDL that was isolated from subjects with homozygous CETP deficiency or who had been treated with high levels of CETP inhibitor (120 mg torcetrapib) had an increased cholesterol efflux potential when matched for unit mass of HDL in media. This correlated with the accumulation of HDL2 species enriched in apolipoprotein E and lecithin-cholesterol acyltransferase. At lower levels of inhibition (60 mg torcetrapib), HDL had a similar ability to promote cholesterol efflux as pretreatment HDL but showed increased cholesterol efflux in parallel with the increase in plasma HDL concentration. Cholesterol efflux measurements appear to correlate with the finding that subjects who attained the highest levels of HDL on torcetrapib showed regression of coronary atheroma as determined by intravascular ultrasound. Although these in vitro measurements may not fully capture the in vivo complexities of HDL metabolism, they suggest that increased HDL attributable to CETP inhibition results in particles that have normal or enhanced ability to promote cholesterol efflux from macrophage foam cells. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104[suppl]:39E-45E)
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