CETP inhibitors revisited

Role of cholesterol ester transfer protein (CETP) in HDL metabolism. HDL matures by the accumulation of phospholipids (PLs) and free cholesterol (FC) from the small intestine, the liver, peripheral tissues, and VLDL/chylomicrons, which is mediated by ABCA1 (ATP-binding cassette subfamily A1) and ABCG1 (ATP-binding cassette subfamily G1) and the enzymes LCAT (lecithin cholesterol acyltransferase) and PLTP (phospholipid transfer protein). CETP mediates the exchange of triglycerides (TGs) and cholesterol esters (CEs) between mature HDL and LDL or VLDL, which is then cleared from the circulation by biliary excretion. CETP inhibitors, e.g. anacetrapib, inhibit CETP, leading to elevated plasma levels of HDL and lower LDL/VLDL. apoA-I, aplipoprotein A-I; SR-BI, scavenger receptor class B, type I; LDLR, LDL receptor.