Functions of cholesterol ester transfer protein and relationship to coronary artery disease risk

The protective role of HDL in atherosclerotic cardiovascular disease reflects in part its ability to promote cholesterol efflux via ATP binding cassette transporters ABCA1 and ABCG1 in macrophage foam cells. This initiates a process of reverse cholesterol transport from the arterial wall to the liver. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL and probably stimulates cholesterol efflux and anti-inflammatory effects in macrophage foam cells but does not increase the overall process of reverse cholesterol transport. Single nucleotide polymorphisms in the CETP gene are associated with lower CETP, higher HDL and probably with reduced CAD. Initial clinical trials with the CETP inhibitor torcetrapib were associated with an adverse outcome that mainly seemed to arise from offtarget toxicity.