Inhibition of cholesterol ester transfer protein by CGS 25159 and changes in lipoproteins in hamsters

Kothari, Himanshu V.; Poirier, Kevin; Lee, Warren H.; Satoh, Yoshitaka

doi:10.1016/s0021-9150(96)05981-3

Cited by 37 publications

(24 citation statements)

References 21 publications

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“…CETP activity has been described as both proatherogenic and antiatherogenic. CETP appears to be proatherogenic in its function of transferring cholesteryl ester from HDL to LDL and VLDL, thus lowering the plasma concentration of HDL-C and raising the concentration of LDL-C and VLDL-C. 13,14,16,28 Paradoxically, CETP has also been proposed to be antiatherogenic in its ability to facilitate the production of small, lipid-poor HDL species that may function to help move cholesterol from peripheral tissues to the liver for catabolism in a process called the reverse cholesterol transport pathway. 29 The epidemiological data concerning the atherogenic potential of CETP activity remain mixed.…”

Section: Discussionmentioning

confidence: 99%

“…CETP functions in the plasma to lower the concentration of HDL-C by moving cholesteryl esters from HDLs to VLDLs and LDLs. 7,10 Transient inhibition of CETP activity in rabbits and hamsters by monoclonal antibodies, 11,12 small molecules, 13 or antisense oligonucleotides 14 causes an increase in plasma HDL-C. Sustained inhibition of CETP expression with antisense oligonucleotides increased plasma HDL-C and reduced atherosclerotic lesions in a rabbit model of atherosclerosis.…”

Section: See Page 2029mentioning

confidence: 99%

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Vaccine-Induced Antibodies Inhibit CETP Activity In Vivo and Reduce Aortic Lesions in a Rabbit Model of Atherosclerosis

Rittershaus

Miller

Thomas

et al. 2000

ATVB

294

152

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Abstract-Using a vaccine approach, we immunized New Zealand White rabbits with a peptide containing a region of cholesteryl ester transfer protein (CETP) known to be required for neutral lipid transfer function. These rabbits had significantly reduced plasma CETP activity and an altered lipoprotein profile. In a cholesterol-fed rabbit model of atherosclerosis, the fraction of plasma cholesterol in HDL was 42% higher and the fraction of plasma cholesterol in LDL was 24% lower in the CETP-vaccinated group than in the control-vaccinated group. Moreover, the percentage of the aorta surface exhibiting atherosclerotic lesion was 39.6% smaller in the CETP-vaccinated rabbits than in controls. The data reported here demonstrate that CETP activity can be reduced in vivo by vaccination with a peptide derived from CETP and support the concept that inhibition of CETP activity in vivo can be antiatherogenic. In addition, these studies suggest that vaccination against a self-antigen is a viable therapeutic strategy for disease management. (Arterioscler

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Section: Discussionmentioning

confidence: 99%

Section: See Page 2029mentioning

confidence: 99%

Vaccine-Induced Antibodies Inhibit CETP Activity In Vivo and Reduce Aortic Lesions in a Rabbit Model of Atherosclerosis

Rittershaus

Miller

Thomas

et al. 2000

ATVB

294

152

View full text Add to dashboard Cite

show abstract

“…In addition to these immunological approaches, several synthetic CETP inhibitors have also been developed. One of the first inhibitors, CGS25159, induced significant decreases in VLDL-c and VLDL-triacylglycerols levels on top of an increase of HDL-c (29%) in normal and hyperlipidemic hamsters at 30 mg/kg/day dosages (85). In 2000, JTT-705, another synthetic CETP inhibitor, was reported to achieve a 50% inhibition of CETP activity in human plasma in vitro at a concentration of 5 M (86).…”

Section: Cetp Inhibition In Animalsmentioning

confidence: 99%

A review of CETP and its relation to atherosclerosis

Grooth

Klerkx

Stroes

et al. 2004

Journal of Lipid Research

235

150

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“…Various successful strategies already have been developed to inhibit plasma CETP activity. [7][8][9] CETP antibodies can inhibit CETP activity and increase HDL-C in hamsters. 10 Also, antisense oligodeoxynucleotides against CETP mRNA, as well as a vaccine that elicits antibodies that block CETP function, lead to significant increases in HDL-C, accompanied by a marked reduction of aortic cholesterol content in rabbits.…”

mentioning

confidence: 99%

Efficacy and Safety of a Novel Cholesteryl Ester Transfer Protein Inhibitor, JTT-705, in Humans

et al. 2002

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Background-Cholesteryl ester transfer protein (CETP) mediates the transfer of neutral lipids between lipoproteins. High plasma levels of CETP are correlated with low HDL cholesterol levels, a strong risk factor for coronary artery disease. In earlier studies, JTT-705, a novel CETP inhibitor, was shown to increase plasma HDL cholesterol and to inhibit the progression of atherosclerosis in cholesterol-fed rabbits. This study describes the first results using this CETP inhibitor in humans. Methods and Results-In a randomized, double-blind, and placebo-controlled trial, we evaluated the efficacy and safety of daily treatment with 300, 600, and 900 mg JTT-705 in 198 healthy subjects with mild hyperlipidemia. Treatment with 900 mg JTT-705 for 4 weeks led to a 37% decrease in CETP activity (PϽ0.0001), a 34% increase in HDL cholesterol (PϽ0.0001), and a 7% decrease in LDL cholesterol (Pϭ0.017), whereas levels of triglycerides, phospholipid transfer protein, and lecithin-cholesterol acyltransferase were unaffected. In line with the increase of total HDL, a rise of HDL 2, HDL 3 , and apolipoprotein A-I was also noted. JTT-705 showed no toxicity with regard to physical examination and routine laboratory tests. Conclusions-We show that the use of the CETP inhibitor JTT-705 in humans is an effective means to raise HDL cholesterol levels with minor gastrointestinal side effects (Pϭ0.06). Although these results hold promise, further studies are needed to investigate whether the observed increase in HDL cholesterol translates into a concomitant reduction in coronary artery disease risk.

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Inhibition of cholesterol ester transfer protein by CGS 25159 and changes in lipoproteins in hamsters

Cited by 37 publications

References 21 publications

Vaccine-Induced Antibodies Inhibit CETP Activity In Vivo and Reduce Aortic Lesions in a Rabbit Model of Atherosclerosis

Vaccine-Induced Antibodies Inhibit CETP Activity In Vivo and Reduce Aortic Lesions in a Rabbit Model of Atherosclerosis

A review of CETP and its relation to atherosclerosis

Efficacy and Safety of a Novel Cholesteryl Ester Transfer Protein Inhibitor, JTT-705, in Humans

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