Cholesterylester transfer protein




Cholesteryl ester transfer protein, plasma
PDB rendering based on 2obd.
Available structures: 2obd
Identifiers
Symbol(s) CETP;
External IDs OMIM: 118470 Homologene: 47904
RNA expression pattern

More reference expression data

Orthologs
Human Mouse
Entrez 1071 na
Ensembl ENSG00000087237 na
Uniprot P11597 na
Refseq NM_000078 (mRNA)
NP_000069 (protein) 		na (mRNA)
na (protein)
Location Chr 16: 55.55 - 55.58 Mb na
Pubmed search [2] na

Cholesteryl ester transfer protein (CETP) (also called plasma lipid transfer protein) is a plasma low density lipoproteins (VLDL or LDL) and exchanges them for cholesteryl esters from high density lipoproteins (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.

Genetics

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

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] However, this mutation also increases the prevalence of coronary heart disease in patients with hypertriglyceridemia.[3] 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.[4]

Pharmacology

As HDL has a protective function in atherosclerosis and cardiovascular disease, and certain disease states (such as the statin) and lower LDL (when co-administered with a statin) in a 2004 study.[6] 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,[7][8] and (in a trial of a combination of torcetrapib and atorvastatin) an increase in cardiovascular events and mortality.[9]

A compound related to torcetrapib, going by the investigative name JTT-705/R1658, is undergoing studies.[10] It increases HDL levels by 30% (as compared to 60% by torcetrapib).[11]. Another CETP inhibitor under development is Merck's MK-0859 anacetrapib, which in initial studies has been shown not to increase blood pressure.[12]

References

  1. ^ a b Zhong S, Sharp DS, Grove JS, Bruce C, Yano K, Curb JD, Tall AR (Jun 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): 2917-23. PMID 8675707.
  2. ^ Barzilai N, Atzmon G, Schechter C, Schaefer EJ, Cupples AL, Lipton R, Cheng S, Shuldiner AR (Oct 2003). "Unique lipoprotein phenotype and genotype associated with exceptional longevity". JAMA 290 (15): 2030-40. PMID 14559957.
  3. ^ Bruce C, Sharp DS, Tall AR (May 1998). "[1]". J Lipid Res 39 (5): 1071-8. PMID 9610775.
  4. ^ Abbey M, Nestel PJ (1994). "Plasma cholesteryl ester transfer protein activity is increased when trans-elaidic acid is substituted for cis-oleic acid in the diet". Atherosclerosis 106 (1): 99–107. doi:10.1016/0021-9150(94)90086-8. PMID 8018112.
  5. ^ Barter PJ, Brewer HB Jr, Chapman MJ, Hennekens CH, Rader DJ, Tall AR (Feb 2003). "Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis". Arterioscler Thromb Vasc Biol 23 (2): 160-7. PMID 12588754.
  6. ^ Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW, Mancuso JP, Rader DJ (Apr 2004). "Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol". N Engl J Med 350 (15): 1505-15. PMID 15071125.
  7. ^ Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, Ruzyllo W, Bachinsky WB, Lasala GP, Tuzcu EM; ILLUSTRATE Investigators (Mar 2007). "Effect of torcetrapib on the progression of coronary atherosclerosis". N Engl J Med 356 (13): 1304-16. PMID 17387129.
  8. ^ Kastelein JJ, van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ, Revkin JH, Grobbee DE, Riley WA, Shear CL, Duggan WT, Bots ML; RADIANCE 1 Investigators. (Apr 2007). "Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia". N Engl J Med 356 (16): 1620-30. PMID 17387131.
  9. ^ U.S. Food and Drug Administration (3 December 2006). "Pfizer Stops All Torcetrapib Clinical Trials in Interest of Patient Safety". Press release.
  10. ^ El Harchaoui K, van der Steeg WA, Stroes ES, Kastelein JJ (Aug 2007). "The role of CETP inhibition in dyslipidemia". Curr Atheroscler Rep 9 (2): 125-33. PMID 17877921.
  11. ^ de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, de Graaf J, Zwinderman AH, Posma JL, van Tol A, Kastelein JJ (May 2002). "Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study". Circulation 105 (18): 2159-65. PMID 11994249.
  12. ^ Reuters. "Merck announces its investigational CETP-Inhibitor, MK-0859, produced positive effects on lipids with no observed blood pressure changes", Reuters, Inc., 4 October 2007. Retrieved on 2007-11-04. 

Further reading

  • Okajima F (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): 480-7. PMID 11915346.
  • Barter PJ, Brewer HB, Chapman MJ, et al. (2003). "Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis.". Arterioscler. Thromb. Vasc. Biol. 23 (2): 160-7. PMID 12588754.
  • Dallinga-Thie GM, Dullaart RP, van Tol A (2007). "Concerted actions of cholesteryl ester transfer protein and phospholipid transfer protein in type 2 diabetes: effects of apolipoproteins.". Curr. Opin. Lipidol. 18 (3): 251-7. doi:10.1097/MOL.0b013e3280e12685. PMID 17495597.
v • d • e
Vitronectin
v • d • e
Membrane transport protein
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Cholesterylester_transfer_protein". A list of authors is available in Wikipedia.