title: Age-related impairment of HDL-mediated cholesterol efflux.
abstract: 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 HDL(3) than HDL(2) (Y-HDL(3), 57.3 +/- 1% vs. E-HDL(3), 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.
authors.affiliation: Research Centre on Aging, Orthopaedic Service, University of Sherbrooke, Sherbrooke, Québec, Canada.
authors.forename: Hicham
authors.initials: H
authors.lastname: Berrougui
authors.forename: Maxim
authors.initials: M
authors.lastname: Isabelle
authors.forename: Martin
authors.initials: M
authors.lastname: Cloutier
authors.forename: Guillaume
authors.initials: G
authors.lastname: Grenier
authors.forename: Abdelouahed
authors.initials: A
authors.lastname: Khalil
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008075:Lipoproteins, HDL; D002784:Cholesterol