• BMB Reports
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• v.28 no.3
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• pp.216-220
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• 1995

cDNA for human cholesteryl ester transfer protein (CETP), a potent atherogenic plasma protein that redistributes the neutral lipids among lipoproteins, was expressed in recombinant vaccinia virus-infected cells (CV-1). Two insertion vectors regulated by different promoters were constructed. The vectors were introduced into human thymidine kinase-negative ($TK^-$) 1438 cells infected with wild-type vaccinia virus (WR strain). Recombinant viruses were selected with 5-bromodeoxyuridine (BUdR) and X-gal and identified with DNA dot blot analysis (vSC11-CETP and vTM1-CETP). The CETP cDNA insert in the recombinant vaccinia virus genome was identified by Southern blot analysis. Transcription of CETP cDNA in CV-1 cells infected with recombinant vaccinia virus was monitored by Northern blot analysis using the CETP cDNA as a probe. Positive signals were detected at 1.8 kb in cells infected with vSC11-CETP and at 2.3 kb in cells infected with vTM1-CETP. The recombinant vaccinia virus-infected CV-1 cells were shown to produce functional CETP when the culture medium was subjected to the CETP assay.

• Journal of Genetic Medicine
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• v.9 no.1
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• pp.38-41
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• 2012

A 32-year-old female patient and her sister show high levels of high density lipoprotein (HDL) cholesterol in regular health checkups, since female patient was 11 years old. The patient's serum total cholesterol was 285 mg/dL and HDL cholesterol was 113 mg/dL. Her sister's total cholesterol was 240 mg/dL and the HDL cholesterol measured to be 90 mg/dL. Lipoprotein pattern and cholesteryl ester transfer activity gene analysis were examined in these patients. We found c.1321+1G>A (IVS14+1G/A) hetero mutation in cholesteryl ester transfer protein (CETP) genes. Generally, CETP mediates transfer and exchange of triglycerides and cholesteryl ester between plasma lipoproteins. Also we investigated a key role of HDL-CE and Apo A-1 metabolism. Patients with low levels of CETP have increased serum HDL levels. We hereby report two Korean cases of CETP deficiency in a family. Brief literature review ensues with the cases.

• Molecules and Cells
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• v.37 no.11
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• pp.777-784
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• 2014

Epidemiologic studies have shown that low-density lipoprotein cholesterol (LDL-C) is a strong risk factor, whilst high-density lipoprotein cholesterol (HDL-C) reduces the risk of coronary heart disease (CHD). Therefore, strategies to manage dyslipidemia in an effort to prevent or treat CHD have primarily attempted at decreasing LDL-C and raising HDL-C levels. Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl ester for triglycerides between HDL and VLDL and LDL. We have published the first report indicating that a group of Japanese patients who were lacking CETP had extremely high HDL-C levels, low LDL-C levels and a low incidence of CHD. Animal studies, as well as clinical and epidemiologic evidences, have suggested that inhibition of CETP provides an effective strategy to raise HDL-C and reduce LDL-C levels. Four CETP inhibitors have substantially increased HDL-C levels in dyslipidemic patients. This review will discuss the current status and future prospects of CETP inhibitors in the treatment of CHD. At present anacetrapib by Merck and evacetrapib by Eli Lilly are under development. By 100mg of anacetrapib HDL-C increased by 138%, and LDL-C decreased by 40%. Evacetrapib 500 mg also showed dramatic 132% increase of HDL-C, while LDL-C decreased by 40%. If larger, long-term, randomized, clinical end point trials could corroborate other findings in reducing atherosclerosis, CETP inhibitors could have a significant impact in the management of dyslipidemic CHD patients. Inhibition of CETP synthesis by antisense oligonucleotide or small molecules will produce more similar conditions to human CETP deficiency and may be effective in reducing atherosclerosis and cardiovascular events. We are expecting the final data of prospective clinical trials by CETP inhibitors in 2015.

• BMB Reports
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• v.28 no.3
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• pp.243-248
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• 1995

Cholesteryl ester transfer protein (CETP), a hydrophobic glycoprotein promoting transfer of cholesteryl esters (CE) from high-density lipoproteins (HDL) to lower-density lipoproteins in the plasma, has been recognized a potent atherogenic factor during the development of coronary artery diseases. This study demonstrated a possible utilization of antisense RNA to inhibit expression of the CETP gene using vaccinia virus as an expression system. The CETP cDNA was inserted into a transfer vector (pSC11) in sense and antisense orientations and used to generate recombinant viruses. Recombinants containing sense or antisense orientations of the CETP cDNA were isolated by $TK^-$ selection and X-gal test. The inserted CETP cDNAs in the recombinants were identified by Southern blot analysis and allowed to transcribe in host cells (CV-1). Expressions of the exogenous CETP mRNA, extracted from the CV-1 cells coinfected with viruses containing sense and antisense DNAs, were monitored by Northern blot analysis using the CETP cDNA probe, by Western blot analysis using monoclonal antibody against the C-terminal active region of the CETP and by the CETP assay. Decreased expressions of the exogenous CETP cDNA were clearly evident in the Northern and Western blot analyses as the dose of antisense expression increased. In the CETP assay, the CETP activities decreased compared to the activity obtained from the cell extracts infected with sense construct only.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.65-65
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• 1995

Cholesteryl Ester Transfer Protein(CETP), a hydrophobic glycoprotein with molecular mass 74KDa, is a lipid transfer protein found in plasma which mediates the transfer of cholesterol ester and triglyceride between high-density lipoprotein (HDL) and other lipoproteins, therefore, it might influence HDL levels. The lipoprotein profile associated with human CETP deficiency (that are two Japanese families, high HDL and low LDL) has low atherogenic potential, raising the possibility that CETP inhibitors can be used as antiatherosclerotic drugs.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.64-64
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• 1995

Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesterol ester and triglyceride between high-density lipoprotein (HDL) and other low-density lipoproteins, therefore, it might influence HDL levels. The levels of HDL is closely related to the atherogenic diseases in human and there were several reports that the trasgenic mice expressing CETP had much worse atherosclerosis than non-expressing control one. Therefore, selective inhibitors of CETP have the potential to be used as antiatherosclerotic agents. Continued screening for potent inhibitors of CETP led to the isolation of Suberitenone B from marine sponge. Suberitenone B, sesterterpenoids of a new skeletal class have been isolated from the sponge Suberites sp. collected from King George Island the Antartic. The structure of the metabolite has been determined by NMR experiments and chemical methods.

• BMB Reports
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• v.35 no.2
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• pp.172-177
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• 2002

We previously reported that cholesteryl ester transfer protein (CETP) inhibitory peptides (designated $P_{28}$ and $P_{10})$ have anti-atherogenic effects in hypercholesterolemic rabbits (Biochim. Biophys. Acta (1998) 1391, 133-144). To further investigate those effects, we studied rabbit plasma that was collected after 30 h of a $P_{28}$ or $P_{10}$ injection. We found that there is a strong correlation between the in vivo CETP inhibition effects and alterations of lipoprotein particle size distribution in rabbit plasma, as determined on an agarose gel electrophoresis and gel filtration column chromatography. In vivo effects of the peptide were observed again in C57BL/6 mice that expressed simian CETP. The $P_{28}$ or $P_{10}$ peptide ($7\;{\mu}g/g$ of body weight) that was dissolved in saline was injected subcutaneously into the mice. The $P_{28}$ injection caused the partial inhibition of plasma CETP activity up to 50%, decreasing the total plasma cholesterol concentration by 30%, and increasing the ratio of HD/total-cholesterol concentration by 150% in the CETP-transgenic (tg) mice. The CETP inhibition by the $P_{28}$ or $P_{10}$ made alterations that modulated the size re-distribution of the lipoproteins in the blood stream. Particle size of the very low (VLDL) and low density lipoproteins (LDL) from the peptide-injected group was highly decreased compared to the saline-injected group (determined on the gel filtration column chromatography). In contrast, The HDL particle size of the $P_{28}$-injected group increased compared to the control group (saline-injected). The expression level of the CETP mRNA of the $P_{28}$-injected CETP-tg mouse appeared lower than the saline-injected CETP-tg mouse. These results suggest that the injection of the CETP inhibitory peptide could affect the CETP expression level in the liver by influencing lipoprotein metabolism.

• Proceedings of the Zoological Society Korea Conference
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• 1996.10a
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• pp.220.1-220
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• 1996

No Abstract, See Full Text

• Preventive Nutrition and Food Science
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• v.1 no.1
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• pp.87-92
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• 1996

This study describes a stable and simple method for the measurement of cholesteryl ester transfer protein(CETP) activities using reconstituted HDL and LDL as substrates. Apolipoproteins (apo) A-I and -B were purified from hog plasma by a new strategy without ultracentrifugation and delipidation. a simple two-step column chromatography was administered. In the first step of phenyl-sepharose CL-4B column chro-matography, hydrophobic plasma proteins were isolated. The most hydrophobic proteins bound to the column appeared to be A-I and apo-B. Contaminat proteins were efficiently eliminated from the sample by washing the column with 0.3M NaCI containing buffer after loading the plasma on the column. Two pure proteins showing each single band on SDS-PSGE of apo A-I and apo-B were individually obtained by a subsequent gel filtration column chromatography(Sephadex G-200). This two-step purification was simple and inexpensive compared to the ultracentrifugation and/or delipidation method that are most commonly used. Reconstituted hight-density lipoproteins(HDL) and low-density lipoproteins(LDL) were prepared using the purified apo A-I and-B, respectively. When these artificially prepared HDL and LDL were used in the assays for CETP as the cholesteryl ester(CE) donor and acceptor respectively, the specific transfer of CE increased up to two fold compared to that used the native HSL and LDL.

• Molecules and Cells
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• v.26 no.4
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• pp.409-414
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• 2008

The cholesteryl ester transfer protein (CETP), a key player in cholesterol metabolism, has been shown to promote the transfer of triglycerides from very low density lipoprotein (VLDL) and low density lipoprotein (LDL) to high density lipoprotein (HDL) in exchange for cholesterol ester. Here we demonstrate that farnesoid X receptor ${\alpha}$ ($FXR{\alpha}$; NR1H4) down-regulates CETP expression in HepG2 cells. A $FXR{\alpha}$ ligand, chenodeoxycholic acid (CDCA), suppressed basal mRNA levels of the CETP gene in HepG2 cells in a dose-dependent manner. Using gel shift and chromatin immunoprecipitation (ChIP) assays, we found that $FXR{\alpha}$ could bind to the liver X receptor ${\alpha}$ ( $LXR{\alpha}$; NR1H3) binding site (LXRE; DR4RE) located within the CETP 5' promoter region. $FXR{\alpha}$ suppressed $LXR{\alpha}$-induced DR4RE-luciferase activity and this effect was mediated by a binding competition between $FXR{\alpha}$ and $LXR{\alpha}$ for DR4RE. Furthermore, the addition of CDCA together with a $LXR{\alpha}$ ligand, GW3965, to HepG2 cells was shown to substantially decrease mRNA levels of hepatic CETP gene, which is typically induced by GW3965. Together, our data demonstrate that $FXR{\alpha}$ down-regulates CETP gene expression via binding to the DR4RE sequence within the CETP 5' promoter and this $FXR{\alpha}$ binding is essential for $FXR{\alpha}$ inhibition of $LXR{\alpha}$-induced CETP expression.