Monoclonal antibody inhibition of cholesteryl ester transfer protein activity in the rabbit. Effects on lipoprotein composition and high density lipoprotein cholesteryl ester metabolism.

Whitlock, Mary E.; Swenson, T L; Ramakrishnan, R.; Leonard, Maurice; Marcel, Yves L.; Milne, Ross W.; Tall, Alan R.

doi:10.1172/jci114132

Cited by 125 publications

(46 citation statements)

References 34 publications

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“…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%

“…Previous work identified this region as containing a "dominant" B-cell epitope of CETP. 20 Monoclonal antibodies that block human, 21 hamster, 22 and rabbit 11 CETP activity have been shown to bind CETP in this region. This 16-amino-acid sequence has been proposed to assume a conformation as an isolated peptide similar to that in the native CETP molecule.…”

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

293

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: See Page 2029mentioning

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

293

152

View full text Add to dashboard Cite

show abstract

“…Genetic alterations in CETP levels in humans and transgenic mice are associated with impairment of important steps involved in reverse cholesterol transport (12). Additionally, elevated CETP levels increase the rate at which cholesteryl ester (CE) returns to the liver (13,14). Although some of these effects are mediated through the actions of circulating CETP, the widespread tissue distribution of CETP mRNA raises the possibility that CETP synthesized by various peripheral tissues may have local functions in lipid metabolism as well.…”

Section: Cholesteryl Ester Transfer Protein (Cetp)mentioning

confidence: 99%

Cholesteryl Ester Transfer Protein Biosynthesis and Cellular Cholesterol Homeostasis Are Tightly Interconnected

Izem

Morton

2001

Journal of Biological Chemistry

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Cholesteryl ester transfer protein (CETP) mediates triglyceride and cholesteryl ester (CE) transfer between lipoproteins, and its activity is strongly modulated by dietary cholesterol. To better understand the regulation of CETP synthesis and the relationship between CETP levels and cellular lipid metabolism, we selected the SW872 adipocytic cell line as a model. These cells secrete CETP in a time-dependent manner at levels exceeding those observed for Caco-2 or HepG2 cells. The addition of LDL, 25OH-cholesterol, oleic acid, or acetylated LDL to SW872 cells increased CETP secretion (activity and mass) up to 6-fold. In contrast, CETP production was decreased by almost 60% after treatment with lipoprotein-deficient serum or ␤-cyclodextrin. These effects, which were paralleled by changes in CETP mRNA, show that CETP biosynthesis in SW872 cells directly correlates with cellular lipid status. To investigate a possible, reciprocal relationship between CETP expression and cellular lipid homeostasis, CETP biosynthesis in SW872 cells was suppressed with CETP antisense oligonucleotides. Antisense oligonucleotides reduced CETP secretion (activity and mass) by 60% compared with sensetreated cells. When CETP synthesis was suppressed for 24 h, triglyceride synthesis was unchanged, but cholesterol biosynthesis was reduced by 20%, and acetate incorporation into CE increased 31%. After 3 days of suppressed CETP synthesis, acetate incorporation into the CE pool increased 3-fold over control. This mirrored a similar increase in CE mass. The efflux of free cholesterol to HDL was the same in sense and antisensetreated cells; however, HDL-induced CE hydrolysis in antisense-treated cells was diminished 2-fold even though neutral CE hydrolase activity was unchanged. Thus, CETP-compromised SW872 cells display a phenotype characterized by inefficient mobilization of CE stores leading to CE accumulation. These results strongly suggest that CETP expression levels contribute to normal cholesterol homeostasis in adipocytic cells.Overall, these studies demonstrate that lipid homeostasis and CETP expression are tightly coupled.

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“…Rabbits are highly susceptible to the development of diet-induced atherosclerosis, and have a naturally high level of CETP. In one study, CETP was inhibited in rabbits by infusing anti-CETP antibodies, which led to a rise in HDL cholesterol ester, and a fall in triglyceride levels (94). Despite this, levels of HDL protein did not change, suggesting a cholesterol ester for triglyceride exchange.…”

Section: Targeting High-density Lipoprotein (Hdl) (Table 2)mentioning

confidence: 99%

Therapeutic modulation of the natural history of coronary atherosclerosis: lessons learned from serial imaging studies

Andrews¹,

Puri²,

Kataoka³

et al. 2016

Cardiovasc. Diagn. Ther.

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Despite advances in risk prediction, preventive and therapeutic strategies, atherosclerotic cardiovascular disease remains a major public health challenge worldwide, carrying considerable morbidity, mortality and health economic burden. There continues to be a need to better understand the natural history of this disease to guide the development of more effective treatment, integral to which is the rapidly evolving field of coronary artery imaging. Various imaging modalities have been refined to enable detailed visualization of the pathological substrate of atherosclerosis, providing accurate and reproducible measures of coronary plaque burden and composition, including the presence of high-risk characteristics. The serial application of such techniques, including coronary computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have uncovered important insights into the progression of coronary plaque over time in patients with stable and unstable coronary artery disease (CAD), and its responsiveness to therapeutic interventions. Here we review the use of different imaging modalities for the surveillance of coronary atherosclerosis and the lessons they have provided about the modulation of CAD by both traditional and experimental therapies.

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Monoclonal antibody inhibition of cholesteryl ester transfer protein activity in the rabbit. Effects on lipoprotein composition and high density lipoprotein cholesteryl ester metabolism.

Cited by 125 publications

References 34 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

Cholesteryl Ester Transfer Protein Biosynthesis and Cellular Cholesterol Homeostasis Are Tightly Interconnected

Therapeutic modulation of the natural history of coronary atherosclerosis: lessons learned from serial imaging studies

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