Cholesterylester Transfer Protein

Cholesterylester transfer protein
Cholesteryl ester transfer protein (CETP), also called

plasma lipid transfer protein, is a plasma protein
that facilitates the transport of cholesteryl esters and
triglycerides between the lipoproteins. 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 heteroexchange, trading a triglyceride for a cholesteryl ester or a
cholesteryl ester for a triglyceride.
levels, most reported an increase in blood pressure,

no change in atherosclerosis,[8][9] and, in a trial of a
combination of torcetrapib and atorvastatin, an increase
in cardiovascular events and mortality.[10]
A compound related to torcetrapib, Dalcetrapib (investigative name JTT-705/R1658), was also being studied,
but trials have since been ceased.[11] It increases HDL levels by 30%, as compared to 60% by torcetrapib.[12] Another CETP inhibitor under development is Mercks MK0859 anacetrapib, which in initial studies is not shown to
increase blood pressure.[13]
Genetics
4 Interactive pathway map
The CETP gene is located on the sixteenth chromosome

(16q21).
Click on genes, proteins and metabolites below to link to

respective articles. [ 1]
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Role in disease
Rare mutations leading to increased function of CETP

have been linked to accelerated atherosclerosis.[1] In contrast, a polymorphism (I405V) of the CETP gene leading to lower serum levels has also been linked to exceptional longevity [2] and to metabolic response to nutritional intervention.[3] However, this mutation also increases the prevalence of coronary heart disease in patients with hypertriglyceridemia.[4] The D442G mutation,
which lowers CETP levels and increases HDL levels also
increases coronary heart disease.[1]
Elaidic acid, a major component of trans fat, increases
CETP activity.[5]
Pharmacology
See also: CETP inhibitor

As HDL can alleviate atherosclerosis and other
cardiovascular diseases, 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.[6] To be specic, 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.[7] Studies
into cardiovascular endpoints, however, were largely
disappointing. While they conrmed the change in lipid
1
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INTERACTIVE PATHWAY MAP
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[[
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|{{{bSize}}}px|alt=Statin Pathway edit|]]
File:StatinPathway_WP430.png
Statin Pathway edit
[1] The interactive pathway map can be edited at WikiPathways: Statin_Pathway_WP430.
5 References
[1] Zhong S, Sharp DS, Grove JS, Bruce C, Yano K, Curb JD
et al. (June 1996). Increased coronary heart disease in
Japanese-American men with mutation in the cholesteryl
ester transfer protein gene despite increased HDL levels.
J Clin Invest 97 (12): 291723. doi:10.1172/JCI118751.
PMC 507389. PMID 8675707.
[2] Barzilai N, Atzmon G, Schechter C, Schaefer EJ, Cupples AL, Lipton R et al. (October 2003). Unique
lipoprotein phenotype and genotype associated with
exceptional longevity. JAMA 290 (15): 203040.
doi:10.1001/jama.290.15.2030. PMID 14559957.
[3] Darabi M, Abolfathi AA, Noori M, Kazemi A, Ostadrahimi A, Rahimipour A et al. (2009). Cholesteryl
ester transfer protein I405V polymorphism inuences
apolipoprotein A-I response to a change in dietary fatty
acid composition. Horm Metab Res 41 (7): 5548.
doi:10.1055/s-0029-1192034. PMID 19242900.
[4] Bruce C, Sharp DS, Tall AR (1 May 1998). Relationship
of HDL and coronary heart disease to a common amino
acid polymorphism in the cholesteryl ester transfer protein
in men with and without hypertriglyceridemia. J Lipid

Res 39 (5): 10718. PMID 9610775.
[5] Abbey M, Nestel PJ (March 1994). Plasma cholesteryl
ester transfer protein activity is increased when transelaidic acid is substituted for cis-oleic acid in the diet.
Atherosclerosis 106 (1): 99107. doi:10.1016/00219150(94)90086-8. PMID 8018112.
[6] Barter PJ, Brewer HB, Chapman MJ, Hennekens CH, Rader DJ, Tall AR (February 2003).
Cholesteryl ester transfer protein:
a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol 23 (2): 1607.
doi:10.1161/01.ATV.0000054658.91146.64.
PMID
12588754.
[7] Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT,
Digenio AG, Clark RW et al. (April 2004). Eects
of an inhibitor of cholesteryl ester transfer protein on
HDL cholesterol. N Engl J Med 350 (15): 150515.
doi:10.1056/NEJMoa031766. PMID 15071125.
[8] Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL,
Duggan WT et al. (March 2007). Eect of torcetrapib
on the progression of coronary atherosclerosis. N Engl J
Med 356 (13): 130416. doi:10.1056/NEJMoa070635.
ISSN 0028-4793. PMID 17387129.
[9] Kastelein JJ, van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ et al. (April 2007). Eect of
torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med 356 (16): 162030.
doi:10.1056/NEJMoa071359. PMID 17387131.
[10] Pzer Stops All Torcetrapib Clinical Trials in Interest of
Patient Safety (Press release). U.S. Food and Drug Administration. 2006-12-03.
[11] El Harchaoui K, van der Steeg WA, Stroes ES, Kastelein
JJ (August 2007). The role of CETP inhibition in
dyslipidemia. Curr Atheroscler Rep 9 (2): 12533.
doi:10.1007/s11883-007-0008-5. PMID 17877921.
[12] de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, de Graaf
J, Zwinderman AH, Posma JL et al. (May 2002).
Ecacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation 105 (18):
215965. doi:10.1161/01.CIR.0000015857.31889.7B.
PMID 11994249.
[13] Reuters (2007-10-04). Merck announces its investigational CETP-Inhibitor, MK-0859, produced positive effects on lipids with no observed blood pressure changes.
Reuters, Inc. Retrieved 26 November 2013.
Further reading
Okajima F (March 2002). "[Distribution of sphingosine 1-phosphate in plasma lipoproteins and its
role in the regulation of the vascular cell functions]".
Tanpakushitsu Kakusan Koso 47 (4 Suppl): 4807.
ISSN 0039-9450. PMID 11915346.
EXTERNAL LINKS
Barter PJ, Brewer HB, Chapman MJ, Hennekens CH, Rader DJ, Tall AR (February
2003).
Cholesteryl ester transfer protein:
a novel target for raising HDL and inhibiting atherosclerosis (Free full text).
Arterioscler. Thromb. Vasc. Biol. 23 (2): 1607.
doi:10.1161/01.ATV.0000054658.91146.64.
ISSN 1079-5642. PMID 12588754.
Dallinga-Thie GM, Dullaart RP, van Tol A (June
2007).
Concerted actions of cholesteryl ester transfer protein and phospholipid transfer protein in type 2 diabetes: eects of apolipoproteins. Curr. Opin. Lipidol. 18 (3): 251
7. doi:10.1097/MOL.0b013e3280e12685. ISSN
0957-9672. PMID 17495597.
7 External links
Cholesterol ester transfer proteins at the US National Library of Medicine Medical Subject Headings (MeSH)
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Cholesterylester Transfer Protein

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Cholesterylester transfer protein

Cholesteryl ester transfer protein (CETP), also called

levels, most reported an increase in blood pressure,

The CETP gene is located on the sixteenth chromosome

Click on genes, proteins and metabolites below to link to

Rare mutations leading to increased function of CETP

See also: CETP inhibitor

INTERACTIVE PATHWAY MAP

top:299px; background:transparent; border-top:3px

in men with and without hypertriglyceridemia. J Lipid

Text and image sources, contributors, and licenses

File:PDB_2obd_EBI.png Source: http://upload.wikimedia.org/wikipedia/commons/1/18/PDB_2obd_EBI.png License: Public domain

Creative Commons Attribution-Share Alike 3.0

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