J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M600167-JLR200 on November 8, 2006

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Journal of Lipid Research, Vol. 48, 328-336, February 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Age-related impairment of HDL-mediated cholesterol efflux

Hicham Berrougui*, Maxim Isabelle*, Martin Cloutier*, Guillaume Grenier*,{dagger} and Abdelouahed Khalil1,*,§

* Research Centre on Aging, Orthopaedic Service, University of Sherbrooke, Sherbrooke, Québec, Canada
{dagger} Department of Surgery, and Geriatric Service, University of Sherbrooke, Sherbrooke, Québec, Canada
§ Department of Medicine, University of Sherbrooke, Sherbrooke, Québec, Canada

Published, JLR Papers in Press, November 8, 2006.

1 To whom correspondence should be addressed. e-mail: abdelouahed.khalil{at}usherbrooke.ca

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 ± 1.4% vs. 49.0 ± 2.2%, respectively; P = 0.013). Reduction in the HDL-mediated cholesterol efflux capacity with aging was more significant with HDL3 than HDL2 (Y-HDL3, 57.3 ± 1% vs. E-HDL3, 50.9 ± 2%; P = 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 ± 2.7 vs. Y-HDL, 40.0 ± 1.9; P = 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.

Supplementary key words aging • reverse cholesterol transport • ATP binding cassette transporter A1 • apolipoprotein A-I • phospholipids • high density lipoproteins


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