Cholesterylester transfer protein

Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein, is a plasma is_associated_with::protein that facilitates the transport of is_associated_with::cholesteryl esters and is_associated_with::triglycerides between the is_associated_with::lipoproteins. It collects triglycerides from very-low-density (VLDL) or is_associated_with::low-density lipoproteins (LDL) and exchanges them for cholesteryl esters from is_associated_with::high-density lipoproteins (HDL), and vice versa. Most of the time, however, CETP does a heteroexchange, trading a triglyceride for a cholesteryl ester or a cholesteryl ester for a triglyceride.

Genetics
The CETP gene is located on the sixteenth is_associated_with::chromosome (16q21).

Role in disease
Rare mutations leading to reduced function of CETP have been linked to accelerated is_associated_with::atherosclerosis. In contrast, a polymorphism (I405V) of the CETP gene leading to lower serum levels has also been linked to exceptional longevity and to metabolic response to nutritional intervention. However, this mutation also increases the prevalence of is_associated_with::coronary heart disease in patients with is_associated_with::hypertriglyceridemia. The D442G mutation, which lowers CETP levels and increases HDL levels also increases coronary heart disease.

is_associated_with::Elaidic acid, a major component of is_associated_with::trans fat, increases CETP activity.

Pharmacology
As HDL can alleviate atherosclerosis and other is_associated_with::cardiovascular diseases, and certain disease states such as the is_associated_with::metabolic syndrome feature low HDL, pharmacological inhibition of CETP is being studied as a method of improving HDL levels. To be specific, in a 2004 study, the small molecular agent is_associated_with::torcetrapib was shown to increase HDL levels, alone and with a is_associated_with::statin, and lower LDL when co-administered with a statin. Studies into cardiovascular endpoints, however, were largely disappointing. While they confirmed the change in is_associated_with::lipid levels, most reported an increase in is_associated_with::blood pressure, no change in atherosclerosis, and, in a trial of a combination of torcetrapib and is_associated_with::atorvastatin, an increase in cardiovascular events and mortality.

A compound related to torcetrapib, is_associated_with::Dalcetrapib (investigative name JTT-705/R1658), was also studied, but trials have ceased. It increases HDL levels by 30%, as compared to 60% by torcetrapib. Another CETP inhibitor under development is Merck's MK-0859 is_associated_with::anacetrapib, which in initial studies did not increase blood pressure.