Cholesterol Efflux, Lecithin−Cholesterol Acyltransferase Activity, and Pre-β Particle Formation by Serum from Human Apolipoprotein A-I and Apolipoprotein A-I/Apolipoprotein A-II Transgenic Mice Consistent with the Latter Being Less Effective for Reverse Cholesterol Transport

Castro, Graciela; Lp, Nihoul; Dengremont, Catherine; C, de Geitère; Delfly, Bernard; Tailleux, Anne; Fiévet, Catherine; Duverger, Nicolas; Denèfle, Patrice; Jc, Fruchart; Em, Rubin

doi:10.1021/bi961191e

Cited by 64 publications

(43 citation statements)

References 26 publications

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“…Consistent with this hypothesis, we identified pre-␤ HDL in significant amounts in human apoA-I-expressing mice, a result previously reported with similar animals. 16,32 Interestingly, the HDL particles of the hA-II mice described in the present study have a size similar to that of apoA-I-containing pre-␤ HDL, but the cholesterol efflux capacity of sera from these animals was similar to that of A-IKO background mice, in which very large HDL particles were observed. This finding indicates that apolipoprotein composition and particle size differently and independently modulate the cholesterol efflux capacity of HDL not only in well-defined reconstituted systems (Guido Franceschini, PhD, unpublished data, 1997), but also in a more physiological experimental setup.…”

Section: Discussionmentioning

confidence: 46%

Human Apolipoproteins A-I and A-II in Cell Cholesterol Efflux

Chiesa

Parolini

Canavesi

et al. 1998

ATVB

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Abstract-The first step in reverse cholesterol transport is the movement of cholesterol out of cells onto lipoprotein acceptors in the interstitial fluid. The contribution of specific lipoprotein components to this process remains to be established. In this study, the role of human apolipoproteins (apo) A-I and A-II in the efflux of cellular cholesterol was investigated in transgenic mouse models in which the expression of murine apoA-I was abolished due to gene targeting (A-IKO). Serum from A-IKO mice and from mice expressing human apoA-I and/or human apoA-II was incubated with [ 3 H]cholesterol-labeled Fu5AH rat hepatoma cells for 4 hours at 37°C. The cholesterol efflux to the serum of A-IKO mice was markedly lower than that to the serum of mice transgenic for human apoA-I (5.0Ϯ1.5% versus 25.0Ϯ4.0%). Expression of human apoA-II alone did not modify the cholesterol efflux capacity of A-IKO mouse serum. Cholesterol efflux to serum of mice expressing human apoA-II together with human apoA-I was significantly lower than that to human apoA-I mouse serum (20.0Ϯ2.3% versus 25.0Ϯ4.0%). Regression analysis of cholesterol efflux versus the lipid/apolipoprotein concentrations of mouse serum suggested that 3 independent factors contribute to determine the cholesterol efflux potential of serum: the apolipoprotein composition of HDL, the serum concentration of HDL phospholipids, and the presence of a small fraction of particles containing apoA-I.

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Section: Discussionmentioning

confidence: 46%

Human Apolipoproteins A-I and A-II in Cell Cholesterol Efflux

Chiesa

Parolini

Canavesi

et al. 1998

ATVB

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“…Both apolipoproteins participate in RCT and promote cholesterol efflux from cultured cells. 1,23,25 In a normal background, new populations of HDLs appeared in the cluster Tg mice. All the human apoA-IV and a proportion of human apoA-I migrated to the pre-␤ position.…”

Section: Vergnes Et Al Human Apoa-i/c-iii/a-iv Cluster Tg Micementioning

confidence: 99%

“…23 Values are reported as the average of at least 3 different determinations. Purified human HDL samples were included in each assay as positive controls.…”

Section: Cholesterol Efflux and Esterification Studiesmentioning

confidence: 99%

“…LCAT activity was determined by use of the exogenous proteoliposome substrate method with 25 L of plasma from female mice. 23 Experiments were repeated twice with 3 and 5 different pools of samples for control and Tg mice, respectively (coefficient of variation Ͻ5%). Cholesterol esterification rate was determined as the decrease in unesterified cholesterol mass (measured enzymatically) during in vitro incubation of whole plasma at 37°C for periods up to 4 hours.…”

Section: Cholesterol Efflux and Esterification Studiesmentioning

confidence: 99%

“…These antibodies showed no crossspecies reactivity. 23 Human apolipoproteins in high-performance-sized exclusion chromatographic (HP-SEC) fractions were quantified by liquidphase double-antibody-based radioimmunoassays, with the use of Tween 20 (0.2% [vol/vol]) to expose cryptic epitopes and polyethylene glycol 8000 (3% [wt/vol]) to enhance reaction kinetics. The primary antisera were polyclonal IgG against delipidated human apolipoproteins (goat anti-apoA-I and goat anti-apoC-III, provided by International Immunology Corp; rabbit anti-apoA-IV 11 ) that displayed insignificant cross-reactivity with their mouse counterparts.…”

Section: Apolipoprotein Quantificationmentioning

confidence: 99%

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Expression of Human Apolipoprotein A-I/C-III/A-IV Gene Cluster in Mice Induces Hyperlipidemia but Reduces Atherogenesis

Vergnes

Baroukh

Ostos

et al. 2000

ATVB

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Abstract-The apolipoprotein (apo)A-I/C-III/A-IV gene cluster is involved in lipid metabolism and atherosclerosis.Overexpression of apoC-III in mice causes hypertriglyceridemia and induces atherogenesis, whereas overexpression of apoA-I or apoA-IV increases cholesterol in plasma high density lipoprotein (HDL) and protects against atherosclerosis. Each gene has been studied alone in transgenic mice but not in combination as the entire cluster. To determine which phenotype is produced by the expression of the entire gene cluster, transgenic mice were generated with a 33-kb human DNA fragment. The results showed that the transgene contained the necessary elements to direct hepatic and intestinal expression of the 3 genes. In the pooled data, plasma concentrations were 257Ϯ9, 7.1Ϯ0.5, and 1.0Ϯ0.2 mg/dL for human apoA-I, apoC-III, and apoA-IV, respectively (meanϮSEM). Concentrations of these apolipoproteins were higher in males than in females. Human apoA-I and apoC-III concentrations were positively correlated, suggesting that they are coregulated. Transgenic mice exhibited gross hypertriglyceridemia and accumulation of apoB 48 -containing triglyceride-rich lipoproteins. Plasma triglyceride and cholesterol concentrations were correlated positively with human apoC-III concentration, and HDL cholesterol was correlated with apoA-I concentration. In an apoE-deficient background, despite being markedly hypertriglyceridemic, cluster transgenic animals compared with nontransgenic animals showed a 61% reduction in atherosclerosis. This suggests that apoA-I and/or apoA-IV can protect against atherosclerosis even in the presence of severe hyperlipidemia. These mice provide a new model for studies of the regulation of the 3 human genes in combination. Key Words: transgenic mice Ⅲ hypertriglyceridemia Ⅲ cholesterol Ⅲ lipoproteins Ⅲ atherosclerosis P lasma lipoproteins influence the development of atherosclerosis, and their concentrations are associated with the risk of coronary heart disease. 1 The genes for 3 apolipoproteins, apoA-I, apoC-III, and apoA-IV, are grouped together in a cluster on 17 kb of human chromosome 11. 2 ApoA-I is the major protein component of HDL. Through its ability to promote cholesterol efflux from cultured cells and to activate lecithin:cholesterol acyltransferase (LCAT), it is involved in reverse cholesterol transport (RCT). 1 Expression of the human apoA-I ( h apoA-I) gene decreases the development of fatty lesions in cholesterol-fed transgenic (Tg) mice 3 and in apoE-deficient (apoE Ϫ/Ϫ ) mice. 4 ApoA-I deficiency in mice did not increase atherogenesis in a normal background 5 but did so in hypercholesterolemic mice expressing human apoB. 6 ApoC-III is a component of HDL and triglyceride-rich lipoproteins (TGRLs). Plasma apoC-III concentration is positively correlated with triglyceride concentration. By inhibiting TGRL catabolism, apoC-III induces hypertriglyceridemia in Tg mice. 7 Expression of the gene was not atherogenic in apoE Ϫ/Ϫ mice. 8 In contrast, h apoC-III expression, in normal or in LDL ...

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Overview of the Measurement of Lipids and Lipoproteins in Mice

Tailleux

Staels

2011

CP Mouse Biology

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Experimental mouse models are widely used for preclinical research on dyslipidemia, atherosclerosis, and cardiometabolic diseases. This unit reports the most commonly used biochemical analysis methods available to determine the lipid and lipoprotein phenotype in the mouse. The discussed methods include: the qualitative and quantitative analysis of lipids, apolipoproteins, and lipoproteins (with a specific emphasis on species-specificities of mice and humans), and the activity assay of major enzymes involved in lipoprotein remodeling (LCAT, PLTP, and LPL). The unit also discusses the most frequently used functional tests to analyze lipid/lipoprotein metabolism in vivo, including triglyceride metabolism, reverse cholesterol transport, intestinal lipid absorption, and secretion. Curr. Protoc. Mouse Biol. 1:265-277 © 2011 by John Wiley & Sons, Inc.

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Cholesterol Efflux, Lecithin−Cholesterol Acyltransferase Activity, and Pre-β Particle Formation by Serum from Human Apolipoprotein A-I and Apolipoprotein A-I/Apolipoprotein A-II Transgenic Mice Consistent with the Latter Being Less Effective for Reverse Cholesterol Transport

Cited by 64 publications

References 26 publications

Human Apolipoproteins A-I and A-II in Cell Cholesterol Efflux

Human Apolipoproteins A-I and A-II in Cell Cholesterol Efflux

Expression of Human Apolipoprotein A-I/C-III/A-IV Gene Cluster in Mice Induces Hyperlipidemia but Reduces Atherogenesis

Overview of the Measurement of Lipids and Lipoproteins in Mice

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