Enhancing apolipoprotein A-I-dependent cholesterol efflux elevates cholesterol export from macrophages in vivo

Mukhamedova, Nigora; Escher, Geneviève; D’Souza, Wilissa; Tchoua, Urbain; Grant, Angela; Krozowski, Zigmund; Bukrinsky, Michael; Sviridov, Dmitri

doi:10.1194/jlr.m800095-jlr200

Cited by 47 publications

(37 citation statements)

References 43 publications

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“…The raw percentages of efflux observed from hASM to both apoAI (4 -14%) and HDL (30 -40%) are also highly consistent with previous reports in other cell types including macrophages (15,22). Recently, Mukhamedova et al (25) using in vitro labeled cells injected into mouse models have shown a correlation between in vitro cholesterol efflux percentages and in vivo reverse cholesterol transport providing evidence that hASM cells potentially function in vivo to regulate reverse cholesterol transport.…”

Section: Discussionsupporting

confidence: 83%

LXR-induced reverse cholesterol transport in human airway smooth muscle is mediated exclusively by ABCA1

Delvecchio¹,

Bilan²,

Nair³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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The association of hypercholesterolemia and obesity with airway hyperresponsiveness has drawn increasing attention to the potential role of cholesterol and lipid homeostasis in lung physiology and in chronic pulmonary diseases such as asthma. We have recently shown that activation of the nuclear hormone receptor liver X receptor (LXR) stimulates cholesterol efflux in human airway smooth muscle (hASM) cells and induces expression of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, members of a family of proteins that mediate reverse cholesterol and phospholipid transport. We show here that ABCA1 is responsible for all LXR-mediated cholesterol and phospholipid efflux to both apolipoprotein AI and high-density lipoprotein acceptors. In contrast, ABCG1 does not appear to be required for this process. Moreover, we show that hASM cells respond to increased levels of cholesterol by inducing expression of ABCA1 and ABCG1 transporters, a process that is dependent on LXR expression. These findings establish a critical role for ABCA1 in reverse cholesterol and phospholipid transport in airway smooth muscle cells and suggest that dysregulation of cholesterol homeostasis in these cells may be important in the pathogenesis of diseases such as asthma.

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Section: Discussionsupporting

confidence: 83%

LXR-induced reverse cholesterol transport in human airway smooth muscle is mediated exclusively by ABCA1

Delvecchio¹,

Bilan²,

Nair³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…8,52 Numerous studies conducted in mice have well demonstrated the determinant role of ABCA1 in prevention of foam cell formation and atherosclerosis development via the promotion of macrophage RCT. [53][54][55][56] In humans, infusion of recombinant apoA-I Milano is associated with a significant regression in atheroma volume in treated patients. 57 Sera from apoA-I milano patient, characterized by a relative abundance of pre-β like HDL particles as compared with large HDL species, have been described to display an increased capacity to remove cholesterol from macrophage through the ABCA1 pathway.…”

Section: Discussionmentioning

confidence: 99%

Elevated CETP Activity Improves Plasma Cholesterol Efflux Capacity From Human Macrophages in Women

Villard

Khoury

Duchêne

et al. 2012

ATVB

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Objective-We aim to identify the impact of endogenous cholesteryl ester transfer protein (CETP) activity on plasma capacity to mediate free cholesterol efflux from human macrophages. Methods and Results-Endogenous plasma CETP activity was measured in a population of 348 women. We defined a low CETP group corresponding to subjects displaying an endogenous plasma CETP activity within the first tertile and a high CETP group corresponding to subjects with an endogenous plasma CETP activity within the third tertile. Subjects from the high CETP activity group displayed a significant increase in the capacity of their plasma (+8.2%; P=0.001) to mediate cholesterol efflux from human acute monocytic leukemia cell line human macrophages and from ATP-binding cassette transporter A1-dependent pathway (+23.4%; P=0.0001) as compared with those from the low CETP activity group. Multivariate analyses revealed that the impact of CETP activity was independent of plasma lipids levels. Pre-β1-high-density lipoprotein concentrations were significantly elevated (+29.6%; P=0.01) in the high CETP activity group as compared with the low CETP activity group. A positive correlation between pre-β1-high-density lipoprotein levels and plasma efflux efficiency from human acute monocytic leukemia cell line human macrophages was observed (r=0.29, P=0.02). Conclusion-CETP

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“…In vivo RCT assay Cholesterol efflux in vivo was measured using a model described by Rader and colleagues [20], with modifications described previously [21]. Briefly, RAW 264.7 macrophage cells were radiolabelled and loaded with cholesterol by incubating with 1.1 GBq/ml [ 3 H]cholesterol and acetylated LDL (50 μg/ml) for 48 h. Cells were washed, incubated for 24 h in serum-free medium, harvested and resuspended in 0.15 mol/l sterile saline at a concentration of 10 7 cells/ml.…”

Section: Methodsmentioning

confidence: 99%

Advanced glycation end-products (AGEs) and functionality of reverse cholesterol transport in patients with type 2 diabetes and in mouse models

et al. 2012

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Aims/hypothesis We investigated the contribution of AGEs to the impairment of reverse cholesterol transport (RCT) variables in diabetic individuals and in two animal models of diabetic obesity and of renal impairment. Methods The capacity of plasma and HDL from 26 individuals with moderately controlled type 2 diabetes to support cholesterol efflux was compared with 26 age-and sexmatched individuals without diabetes. We also compared the rates of RCT in vivo in two animal models: db/db mice and mice with chronic renal failure. Results Diabetic individuals had characteristic dyslipidaemia and higher levels of plasma AGEs. The capacity of whole plasma, ApoB-depleted plasma and isolated HDL to support cholesterol efflux was greater for diabetic patients compared with controls despite their lower HDL-cholesterol levels. The capacity of plasma to support cholesterol efflux correlated with plasma levels of cholesteryl ester transfer protein and levels of ApoB, but not with levels of AGE. RCT was severely impaired in db/db mice despite elevated HDL-cholesterol levels and no change in AGE concentration, whereas RCT in uraemic mice was unaffected despite elevated AGE levels. Conclusions/interpretation AGEs are unlikely to contribute significantly to the impairment of RCT in type 2 diabetes.

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Enhancing apolipoprotein A-I-dependent cholesterol efflux elevates cholesterol export from macrophages in vivo

Cited by 47 publications

References 43 publications

LXR-induced reverse cholesterol transport in human airway smooth muscle is mediated exclusively by ABCA1

LXR-induced reverse cholesterol transport in human airway smooth muscle is mediated exclusively by ABCA1

Elevated CETP Activity Improves Plasma Cholesterol Efflux Capacity From Human Macrophages in Women

Advanced glycation end-products (AGEs) and functionality of reverse cholesterol transport in patients with type 2 diabetes and in mouse models

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