The effects of cholesterol ester transfer protein inhibition on cholesterol efflux

Alan R Tall
American Journal of Cardiology 2009 November 16, 104 (10 Suppl): 39E-45E
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 HDL(2) 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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"