Cellular Cholesterol Transport and Efflux in Fibroblasts Are Abnormal in Subjects With Familial HDL Deficiency

Marcil, Michel; Yu, Lu; Krimbou, Larbi; Boucher, Betsie; Oram, John F.; Cohn, Jeffrey S.; Genest, Jacques

doi:10.1161/01.atv.19.1.159

Cited by 84 publications

(79 citation statements)

References 62 publications

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“…HDL-mediated cholesterol efflux capacity has been demonstrated to be reduced in diabetes (46), in subjects with familial HDL deficiency (47), and in Tangier disease (48) and has been associated with an alteration in HDL concentration, distribution, or composition and structure. In vitro studies have shown that HDL-mediated cholesterol efflux is impaired by whole cigarette smoke extracts through lipid peroxidation (49).…”

Section: Discussionmentioning

confidence: 99%

Age-related impairment of HDL-mediated cholesterol efflux

Berrougui

Isabelle

Cloutier

et al. 2007

Journal of Lipid Research

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Our aim in this study was to investigate the effect of aging on the capacity of HDLs to promote reverse cholesterol transport. HDLs were isolated from plasma of young (Y-HDL) and elderly (E-HDL) subjects. HDL-mediated cholesterol efflux was studied using THP-1 and J774 macrophages. Our results show that E-HDLs present a lower capacity to promote cholesterol efflux than Y-HDLs (41.7 6 1.4% vs. 49.0 6 2.2%, respectively; P 5 0.013). Reduction in the HDL-mediated cholesterol efflux capacity with aging was more significant with HDL 3 than HDL 2 (Y-HDL 3 , 57.3 6 1% vs. E-HDL 3 , 50.9 6 2%; P 5 0.012). Moreover, our results show that ABCA1-mediated cholesterol efflux is the more affected pathway in terms of cholesterol-removing capacity. Interestingly, the composition and structure of HDL revealed a reduction in the phosphatidylcholine-sphingomyelin ratio (E-HDL, 32.7 6 2.7 vs. Y-HDL, 40.0 6 1.9; P 5 0.029) and in the phospholipidic layer membrane fluidity in E-HDL compared with Y-HDL as well as an alteration in the apolipoprotein A-I structure and charge. In conclusion, our results shown that E-HDLs present a reduced capacity to promote cholesterol efflux, principally through the ABCA1 pathway, and this may explain the increase of the incidence of cardiovascular diseases observed during aging.-Berrougui, H., M. Isabelle, M. Cloutier, G. Grenier, and A. Khalil. Age-related impairment of HDL-mediated cholesterol efflux. J. Lipid Res. 2007. 48: 328-336.

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Section: Discussionmentioning

confidence: 99%

Age-related impairment of HDL-mediated cholesterol efflux

Berrougui

Isabelle

Cloutier

et al. 2007

Journal of Lipid Research

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“…The efflux of cholesterol from cells is mediated predominantly by ABCA1, which is a member of the ATP binding cassette transporter superfamily that contains 12 putative transmembrane domains and two ABCs (13,14). The importance of ABCA1 is shown by Tangier disease, in which ABCA1 deficiency results in the accumulation of cholesteryl esters in various tissues and clinically shows markedly enlarged yellow tonsils and very low HDL cholesterol levels (15)(16)(17)(18). ABCA1 promotes the transport of cholesterol and phospholipids across cell membranes, where these lipids then complex with acceptor particles, such as apolipoprotein A-I, leading to HDL formation (14), thereby reg-ulating cellular cholesterol homeostasis (19).…”

mentioning

confidence: 99%

Regulation of ABCA1 expression in human keratinocytes and murine epidermis

Jiang

Lü

Kim

et al. 2006

Journal of Lipid Research

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Keratinocytes require abundant cholesterol for cutaneous permeability barrier function; hence, the regulation of cholesterol homeostasis is of great importance. ABCA1 is a membrane transporter responsible for cholesterol efflux and plays a pivotal role in regulating cellular cholesterol levels. We demonstrate that ABCA1 is expressed in cultured human keratinocytes (CHKs) and murine epidermis. Liver X receptor (LXR) activation markedly stimulates ABCA1 mRNA and protein levels in CHKs and mouse epidermis. In addition to LXR, activators of peroxisome proliferator-activated receptor (PPAR)a, PPARb/d, and retinoid X receptor (RXR), but neither PPARg nor retinoic acid receptor, also increase ABCA1 expression in CHKs. Increases in cholesterol supply induced by LDL or mevalonate stimulate ABCA1 expression, whereas inhibiting cholesterol synthesis with statins or cholesterol sulfate decreases ABCA1 expression in CHKs. After acute permeability barrier disruption by either tape-stripping or acetone treatment, ABCA1 expression declines, and this attenuates cellular cholesterol efflux, making more cholesterol available for regeneration of the barrier. In addition, during fetal epidermal development, ABCA1 expression decreases at days 18-22 of gestation (term 5 22 days), leaving more cholesterol available during the critical period of barrier formation. Together, our results show that ABCA1 is expressed in keratinocytes, where it is negatively regulated by a decrease in cellular cholesterol levels or altered permeability barrier requirements and positively regulated by activators of LXR, PPARs, and RXR or increases in cellular cholesterol levels.-Jiang, Y. J., B. Lu, P. Kim, P. M. Elias, and K. R. Feingold. Regulation of ABCA1 expression in human keratinocytes and murine epidermis.

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“…Japanese-AmericanslivingintheUnitedStatesaregeneti-thesumoftheradioactivityinthemediaandcells 28) . Theabilityofindividualserumtopromotecholesterol efflux was calculated by subtracting values obtained withoutserum inorder toexclude theeffects of passivediffusion.Tominimizeintra-assayvariability,each serum sample was run in triplicate, and the average andstandarddeviationvalueswerecalculatedforeach percent of efflux obtained.…”

Section: Biochemical Analysesmentioning

confidence: 99%

Relationship between Serum Cholesterol Efflux Capacity and Glucose Intolerance in Japanese-Americans

Kubota

Nakanishi

Hirano

et al. 2014

JAT

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Aim: Serum cholesterol efflux has been suggested to be a key anti-atherogenic function of reverse cholesterol transport. Meanwhile, the quantitative and qualitative alteration of the levels of lipoproteins in the serum has been reported in patients with diabetes, although it remains unclear whether the serum cholesterol efflux capacity is impaired in cases of newly diagnosed glucose intolerance. We thus assessed the relationship between the serum cholesterol efflux capacity and glucose intolerance as detected using oral glucose tolerance tests (OGTTs). Methods: We measured the capacity of whole serum to mediate cholesterol efflux from human THP-1 macrophages in a cohort of 439 Japanese-Americans who underwent 75-g OGTTs. A multiple regression analysis was performed to examine the relationship between the serum cholesterol efflux capacity and glucose intolerance. Results: The serum cholesterol efflux capacity was found to be negatively correlated with the area under the curve for the serum glucose concentration during the 75-g OGTTs in all subjects. In addition, the serum cholesterol efflux capacity was found to be modestly but significantly lower in the glucose intolerance group (31.4±6.2%) than in the normal glucose tolerance group (33.2±6.1%). There was also a negative association between the serum cholesterol efflux capacity and glucose intolerance after adjusting for age and sex. Moreover, this association remained significant even after further adjustments for serum total cholesterol, high-density lipoprotein cholesterol, apolipoprotein AI and C-reactive protein. Conclusions:The serum cholesterol efflux capacity is impaired in Japanese-Americans newly diagnosed with glucose intolerance. This impairment may contribute in some manner to increasing the risk of atherosclerotic disease in subjects with glucose intolerance.

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Cellular Cholesterol Transport and Efflux in Fibroblasts Are Abnormal in Subjects With Familial HDL Deficiency

Cited by 84 publications

References 62 publications

Age-related impairment of HDL-mediated cholesterol efflux

Age-related impairment of HDL-mediated cholesterol efflux

Regulation of ABCA1 expression in human keratinocytes and murine epidermis

Relationship between Serum Cholesterol Efflux Capacity and Glucose Intolerance in Japanese-Americans

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