CER-001, a HDL-mimetic, stimulates the reverse lipid transport and atherosclerosis regression in high cholesterol diet-fed LDL-receptor deficient mice

Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Ackermann, Rose; Sy, Gavin; Bluteau, Alice; Cholez, Guy; Keyserling, Constance H.; Lalwani, Narendra D.; Paolini, John F.; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

doi:10.1016/j.atherosclerosis.2013.10.018

Cited by 93 publications

(69 citation statements)

References 46 publications

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“…Similar effects have been reported upon apoA-I infusion in experimental models (29)(30)(31). The VLDL-c increase in response to apoA-I infusion has been attributed to both increased CETP-mediated cholesterol exchange between HDL-c and VLDL-c leading to higher VLDL-c, as well as to enhanced hepatic VLDL production refl ecting an increased cholesterol fl ux toward the liver ( 29,31 ).…”

Section: Plasma Lipid Changes Following Cer-001 Infusionsupporting

confidence: 61%

Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA

Kootte

Smits

Valk

et al. 2015

Journal of Lipid Research

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The large residual burden of CVD in patients receiving guideline-based medical treatment, underscores the need for additional therapeutic interventions ( 1 ). Strategies aimed at increasing HDL-cholesterol (HDL-c) have been pursued as a promising target in CVD prevention for more than two decades ( 2, 3 ), albeit without a clear CVD benefi t. Both the cholesteryl ester transfer protein (CETP) inhibitors ( 4 ) and nicotinic acid derivatives ( 5 ), increasing HDL-c on top of standard-of-care by 25-40%, have failed to reduce CVD risk. The expectation of HDL-c as an F-fl uorodeoxyglucose; FHA, familial hypoalphalipoproteinemia; FNS, fecal neutral sterol; FSE, fecal sterol excretion; HDL-c, HDL-cholesterol; IQR, interquartile range; LDL-c, LDL-cholesterol; MVWA, mean vessel wall area; PET/CT, positron emission tomography/computed tomography; RCT, reverse cholesterol transport; ROI, region of interest; SUV max , maximal standardized uptake value; 3T, 3.0 Tesla; TBR max , maximal target-to-background ratio; VLDL-c, VLDLcholesterol.

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Section: Plasma Lipid Changes Following Cer-001 Infusionsupporting

confidence: 61%

Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA

Kootte

Smits

Valk

et al. 2015

Journal of Lipid Research

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“…Intravenous infusions of HDL, HDL-like particles, and delipidated apoA-I have been reported to be effective in reducing atherosclerotic lesions in animal models ( 21 ) although the results have been less robust in human studies ( 22 ). The current report and work by the Fogelman group have raised the exciting possibility of a future orally available agent targeted at improving HDL function, likely through a gut-mediated mechanism of action.…”

mentioning

confidence: 88%

Mimetic peptides of human apoA-I helix 10 get together to lower lipids and ameliorate atherosclerosis: is the action in the gut?

Wool

Reardon

Getz

2014

Journal of Lipid Research

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“…A POPC was fi rst used in ETC-216 (rApoA-I-Milano), and then a mixture of 1,2-dipalmitoyl-sn -glycero-3-phosphocholine (DPPC) and SM was used for ETC-642, a peptide-based rHDL ( 17,19 ). Most recently, SM was used in CER-001, another newly developed rApoA-I-based rHDL ( 20 ). Both SM and saturated fatty acid-containing lipids like DPPC have superior cholesterol binding capacity relative to unsaturated POPC and soyPC ( 21,22 ).…”

Section: Plasma Hdl Remodelingmentioning

confidence: 99%

The effect of phospholipid composition of reconstituted HDL on its cholesterol efflux and anti-inflammatory properties

Schwendeman

Sviridov

Yuan

et al. 2015

Journal of Lipid Research

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Infusions of cholesterol-free reconstituted HDL (rHDL) particles have been shown to rapidly reverse atherosclerosis in a wide variety of animal models and in clinical trials of acute coronary syndrome patients ( 1-5 ). While a significant emphasis has been placed on investigating the HDL protein component, i.e., ApoA-I, ApoA-I mutants, and mimetic peptides, the importance of HDL phospholipid (PL) composition has not been systematically investigated. Lipid represents 50-80% of the total HDL mass and is known to affect particle stability in vivo, cholesterol effl ux from macrophages, the ability to interact with LCAT, and cholesterol elimination ( 6-11 ). Lipid composition also largely defi nes the size, net charge, and rigidity of the rHDL particles; all are important factors in the pharmacokinetic and pharmacodynamic properties of rHDL. The investigation of the effects of lipid composition on the resulting rHDL properties in vitro and in vivo is the focus of this article. By better defi ning the lipid effect of rHDL, we hope to be able to favorably alter the potency and safety of rHDL, and ultimately advance clinical translation of these potentially life-changing nanomedicines.The PL composition of endogenous HDL contains phosphatidylcholines (PCs), SM, and small amounts of lysophosphatidylcholine (LPC), phosphatidylethanolamine, Abstract The goal of this study was to understand how the reconstituted HDL (rHDL) phospholipid (PL) composition affects its cholesterol effl ux and anti-infl ammatory properties. An ApoA-I mimetic peptide, 5A, was combined with either SM or POPC. Both lipid formulations exhibited similar in vitro cholesterol effl ux by ABCA1, but 5A-SM exhibited higher ABCG1-and SR-BI-mediated effl ux relative to 5A-POPC ( P < 0.05). Injection of both rHDLs in rats resulted in mobilization of plasma cholesterol, although the relative potency was 3-fold higher for the same doses of 5A-SM than for 5A-POPC. Formation of pre ␤ HDL was observed following incubation of rHDLs with both human and rat plasma in vitro, with 5A-SM inducing a higher extent of pre ␤ formation relative to 5A-POPC. Both rHDLs exhibited antiinfl ammatory properties, but 5A-SM showed higher inhibition of TNF-␣ , IL-6, and IL-1 ␤ release than did 5A-POPC ( P < 0.05). Both 5A-SM and 5A-POPC showed reduction in total plaque area in ApoE ؊ / ؊ mice, but only 5A-SM showed a statistically signifi cant reduction over placebo control and baseline ( P < 0.01). The type of PL used to reconstitute peptide has signifi cant infl uence on rHDL's anti-infl ammatory and anti-atherosclerosis properties.

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CER-001, a HDL-mimetic, stimulates the reverse lipid transport and atherosclerosis regression in high cholesterol diet-fed LDL-receptor deficient mice

Cited by 93 publications

References 46 publications

Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA

Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA

Mimetic peptides of human apoA-I helix 10 get together to lower lipids and ameliorate atherosclerosis: is the action in the gut?

The effect of phospholipid composition of reconstituted HDL on its cholesterol efflux and anti-inflammatory properties

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