Cholesterylester transfer protein
Encyclopedia
Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein
, is a plasma
protein
that facilitates the transport of cholesteryl ester
s and triglyceride
s between the lipoprotein
s. It collects triglycerides from very-low-density (VLDL) or low-density lipoproteins (LDL) and exchanges them for cholesteryl esters from high-density lipoproteins (HDL), and vice versa. Most of the time, however, CETP does a homoexchange, trading a triglyceride for a triglyceride or a cholesteryl ester for a cholesteryl ester.
. 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 coronary heart disease in patients with hypertriglyceridemia. The D442G mutation, which lowers CETP levels and increases HDL levels also increases coronary heart disease.
Elaidic acid
, a major component of trans fat
, increases CETP activity.
s, and certain disease states such as the 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 torcetrapib
was shown to increase HDL levels, alone and with a statin
, and lower LDL when co-administered with a statin. Studies into cardiovascular endpoints, however, were largely disappointing. While they confirmed the change in lipid levels, most reported an increase in blood pressure
, no change in atherosclerosis, and, in a trial of a combination of torcetrapib and atorvastatin
, an increase in cardiovascular events and mortality.
A compound related to torcetrapib, with the investigative name JTT-705/R1658, is also being studied. It increases HDL levels by 30%, as compared to 60% by torcetrapib. Another CETP inhibitor under development is Merck's MK-0859 anacetrapib
, which in initial studies is not shown to increase blood pressure.
Lipid transfer proteins
Plant lipid transfer proteins, also known as plant LTPs or PLTPs, are a group of highly-conserved proteins of about 9kDa found in higher plant tissues. As its name implies, lipid transfer proteins are responsible for the shuttling of phospholipids and other fatty acid groups between cell membranes...
, is a plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that facilitates the transport of cholesteryl ester
Cholesteryl ester
A cholesteryl ester is, as its name would imply, an ester of cholesterol. The ester bond is formed between the carboxylate group of a fatty acid and the hydroxyl group of cholesterol. Cholesteryl Esters have a lower solubility in water than Cholesterol and, in other words, are more hydrophobic...
s and triglyceride
Triglyceride
A triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....
s between the lipoprotein
Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
s. It collects triglycerides from very-low-density (VLDL) or low-density lipoproteins (LDL) and exchanges them for cholesteryl esters from high-density lipoproteins (HDL), and vice versa. Most of the time, however, CETP does a homoexchange, trading a triglyceride for a triglyceride or a cholesteryl ester for a cholesteryl ester.
Role in disease
Rare mutations leading to increased function of CETP have been linked to accelerated atherosclerosisAtherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
. 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 coronary heart disease in patients with hypertriglyceridemia. The D442G mutation, which lowers CETP levels and increases HDL levels also increases coronary heart disease.
Elaidic acid
Elaidic acid
Elaidic acid is the major trans fat found in hydrogenated vegetable oils and occurs in small amounts in caprine and bovine milk . It is the trans isomer of oleic acid. The name of the elaidinization reaction comes from elaidic acid.Elaidic acid increases CETP activity, which in turn raises VLDL...
, a major component of trans fat
Trans fat
Trans fat is the common name for unsaturated fat with trans-isomer fatty acid. Because the term refers to the configuration of a double carbon-carbon bond, trans fats are sometimes monounsaturated or polyunsaturated, but never saturated....
, increases CETP activity.
Pharmacology
As HDL can alleviate atherosclerosis and other cardiovascular diseaseCardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
s, and certain disease states such as the metabolic syndrome
Metabolic syndrome
Metabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
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 torcetrapib
Torcetrapib
Torcetrapib was a drug being developed to treat hypercholesterolemia and prevent cardiovascular disease...
was shown to increase HDL levels, alone and with a statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
, and lower LDL when co-administered with a statin. Studies into cardiovascular endpoints, however, were largely disappointing. While they confirmed the change in lipid levels, most reported an increase in blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, no change in atherosclerosis, and, in a trial of a combination of torcetrapib and atorvastatin
Atorvastatin
Atorvastatin , sold by Pfizer under the trade name Lipitor, is a member of the drug class known as statins, used for lowering blood cholesterol. It also stabilizes plaque and prevents strokes through anti-inflammatory and other mechanisms...
, an increase in cardiovascular events and mortality.
A compound related to torcetrapib, with the investigative name JTT-705/R1658, is also being studied. It increases HDL levels by 30%, as compared to 60% by torcetrapib. Another CETP inhibitor under development is Merck's MK-0859 anacetrapib
Anacetrapib
Anacetrapib is a CETP inhibitor being developed to treat hypercholesterolemia and prevent cardiovascular disease.-Clinical trials:...
, which in initial studies is not shown to increase blood pressure.