Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis - PubMed (original) (raw)
Review
Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis
Philip J Barter et al. Arterioscler Thromb Vasc Biol. 2003.
Abstract
Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters from antiatherogenic HDLs to proatherogenic apolipoprotein B (apoB)-containing lipoproteins, including VLDLs, VLDL remnants, IDLs, and LDLs. A deficiency of CETP is associated with increased HDL levels and decreased LDL levels, a profile that is typically antiatherogenic. Studies in rabbits, a species with naturally high levels of CETP, support the therapeutic potential of CETP inhibition as an approach to retarding atherogenesis. Studies in mice, a species that lacks CETP activity, have provided mixed results. Human subjects with heterozygous CETP deficiency and an HDL cholesterol level >60 mg/dL have a reduced risk of coronary heart disease. Evidence that atherosclerosis may be increased in CETP-deficient subjects whose HDL levels are not increased is difficult to interpret and may reflect confounding or bias. Small-molecule inhibitors of CETP have now been tested in human subjects and shown to increase the concentration of HDL cholesterol while decreasing that of LDL cholesterol and apoB. Thus, it seems important and timely to test the hypothesis in randomized trials of humans that pharmacological inhibition of CETP retards the development of atherosclerosis.
Comment in
- Is there a need for cholesteryl ester transfer protein inhibition?
Parini P, Rudel LL. Parini P, et al. Arterioscler Thromb Vasc Biol. 2003 Mar 1;23(3):374-5. doi: 10.1161/01.ATV.0000060447.25136.1C. Arterioscler Thromb Vasc Biol. 2003. PMID: 12639826 No abstract available.
Similar articles
- Pharmacological modulation of cholesteryl ester transfer protein, a new therapeutic target in atherogenic dyslipidemia.
Le Goff W, Guerin M, Chapman MJ. Le Goff W, et al. Pharmacol Ther. 2004 Jan;101(1):17-38. doi: 10.1016/j.pharmthera.2003.10.001. Pharmacol Ther. 2004. PMID: 14729390 Review. - Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation.
Inazu A, Brown ML, Hesler CB, Agellon LB, Koizumi J, Takata K, Maruhama Y, Mabuchi H, Tall AR. Inazu A, et al. N Engl J Med. 1990 Nov 1;323(18):1234-8. doi: 10.1056/NEJM199011013231803. N Engl J Med. 1990. PMID: 2215607 - A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits.
Okamoto H, Yonemori F, Wakitani K, Minowa T, Maeda K, Shinkai H. Okamoto H, et al. Nature. 2000 Jul 13;406(6792):203-7. doi: 10.1038/35018119. Nature. 2000. PMID: 10910363 - Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease.
Barter PJ, Kastelein JJ. Barter PJ, et al. J Am Coll Cardiol. 2006 Feb 7;47(3):492-9. doi: 10.1016/j.jacc.2005.09.042. Epub 2006 Jan 18. J Am Coll Cardiol. 2006. PMID: 16458126 Review. - Cholesteryl ester transfer protein TaqI B2B2 genotype is associated with higher HDL cholesterol levels and lower risk of coronary heart disease end points in men with HDL deficiency: Veterans Affairs HDL Cholesterol Intervention Trial.
Brousseau ME, O'Connor JJ Jr, Ordovas JM, Collins D, Otvos JD, Massov T, McNamara JR, Rubins HB, Robins SJ, Schaefer EJ. Brousseau ME, et al. Arterioscler Thromb Vasc Biol. 2002 Jul 1;22(7):1148-54. doi: 10.1161/01.atv.0000024566.57589.2e. Arterioscler Thromb Vasc Biol. 2002. PMID: 12117730 Clinical Trial.
Cited by
- Tissue specificity-aware TWAS (TSA-TWAS) framework identifies novel associations with metabolic, immunologic, and virologic traits in HIV-positive adults.
Li B, Veturi Y, Verma A, Bradford Y, Daar ES, Gulick RM, Riddler SA, Robbins GK, Lennox JL, Haas DW, Ritchie MD. Li B, et al. PLoS Genet. 2021 Apr 26;17(4):e1009464. doi: 10.1371/journal.pgen.1009464. eCollection 2021 Apr. PLoS Genet. 2021. PMID: 33901188 Free PMC article. - Constitutive inhibition of plasma CETP by apolipoprotein C1 is blunted in dyslipidemic patients with coronary artery disease.
Pillois X, Gautier T, Bouillet B, Pais de Barros JP, Jeannin A, Vergès B, Bonnet J, Lagrost L. Pillois X, et al. J Lipid Res. 2012 Jun;53(6):1200-9. doi: 10.1194/jlr.M022988. Epub 2012 Apr 2. J Lipid Res. 2012. PMID: 22474067 Free PMC article. - Crystal structures of cholesteryl ester transfer protein in complex with inhibitors.
Liu S, Mistry A, Reynolds JM, Lloyd DB, Griffor MC, Perry DA, Ruggeri RB, Clark RW, Qiu X. Liu S, et al. J Biol Chem. 2012 Oct 26;287(44):37321-9. doi: 10.1074/jbc.M112.380063. Epub 2012 Sep 7. J Biol Chem. 2012. PMID: 22961980 Free PMC article. - Obstructive Sleep Apnoea and Lipid Metabolism: The Summary of Evidence and Future Perspectives in the Pathophysiology of OSA-Associated Dyslipidaemia.
Meszaros M, Bikov A. Meszaros M, et al. Biomedicines. 2022 Oct 29;10(11):2754. doi: 10.3390/biomedicines10112754. Biomedicines. 2022. PMID: 36359273 Free PMC article. Review. - Regulation of reverse cholesterol transport - a comprehensive appraisal of available animal studies.
Annema W, Tietge UJ. Annema W, et al. Nutr Metab (Lond). 2012 Mar 29;9(1):25. doi: 10.1186/1743-7075-9-25. Nutr Metab (Lond). 2012. PMID: 22458435 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Miscellaneous