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What is CETP?

Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein secreted by the liver that mediates the transfer of cholesteryl esters and triglycerides between lipoproteins.1,2

Its curved tunnel structure directly transfers cholesteryl esters from antiatherogenic high-density lipoproteins (HDLs) to proatherogenic low-density lipoproteins (LDLs).1-4

As a result of this transfer, CETP promotes increased levels of LDL-C, which can lead to more plaque deposits.5,6

A graph showing how CETP works with HDL and LDL. First, CETP curves against HDL. Then, CETP penetrates HDL surface. Lastly, CETP directly transfers cholesteryl esters from HDL to LDL.
A close-up of blood cellsA close-up of blood cells

CETP and Cardiovascular Disease

Studies have shown that individuals who have genetically lower levels of CETP activity
have fewer cardiovascular events.7-11

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1. Barter PJ, Rye KA. Cholesteryl ester transfer protein inhibition as a strategy to reduce cardiovascular risk. J Lipid Res. 2012;53(9):1755-1766. doi:10.1194/jlr.R024075 2. Kastelein JJP, Hsieh A, Dicklin MR, Ditmarsch M, Davidson MH. Obicetrapib: reversing the tide of CETP inhibitor disappointments. Curr Atheroscler Rep. 2024;26(2):35-44. doi:10.1007/s11883-023-01184-1 3. Zhang M, Lei D, Peng B, et al. Assessing the mechanisms of cholesteryl ester transfer protein inhibitors. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862(12):1606-1617. doi:10.1016/j.bbalip.2017.09.004 4. Hesler CB, Swenson TL, Tall AR. Purification and characterization of a human plasma cholesteryl ester transfer protein. J Biol Chem. 1987;262(5):2275-2282. 5. Ivanova EA, Myasoedova VA, Melnichenko AA, Grechko AV, Orekhov AN. Small dense low-density lipoprotein as biomarker for atherosclerotic diseases. Oxid Med Cell Longev. 2017;2017:1273042. doi:10.1155/2017/1273042 6. Hirano T, Kodera R, Hirashima T, et al. Metabolic properties of low-density lipoprotein (LDL) triglycerides in patients with type 2 diabetes, comparison with small dense LDL-cholesterol. J Atheroscler Thromb. 2022;29(5):762-774. doi:10.5551/jat.62789 7. Johannsen TH, Frikke-Schmidt R, Schou J, Nordestgaard BG, Tybjærg-Hansen A. Genetic inhibition of CETP, ischemic vascular disease and mortality, and possible adverse effects. J Am Coll Cardiol. 2012;60(20):2041-2048. doi:10.1016/j.jacc.2012.07.045 8. Ference BA, Kastelein JJP, Ginsberg HN, et al. Association of genetic variants related to CETP inhibitors and statins with lipoprotein levels and cardiovascular risk. JAMA. 2017;318(10):947-956. doi:10.1001/jama.2017.11467 9. Thompson A, Di Angelantonio E, Sarwar N, et al. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA. 2008;299(23):2777-2788. doi:10.1001/jama.299.23.2777 10. Voight BF, Peloso GM, Orho-Melander M, et al. Plasma HDL cholesterol and risk of myocardial infarction: a Mendelian randomisation study. Lancet. 2012;380(9841):572-580. doi:10.1016/S0140-6736(12)60312-2 11. Nomura A, Won HH, Khera AV, et al. Protein-truncating variants at the cholesteryl ester transfer protein gene and risk for coronary heart disease. Circ Res. 2017;121(1):81-88. doi:10.1161/CIRCRESAHA.117.311145