Submitted on April 11, 2006
Revised on October 30, 2006
Accepted on November 8, 2006
Age-related impairment of HDL-mediated cholesterol efflux
Hicham Berrougui, Maxim Isabelle, Martin Cloutier, Guillaume Grenier, and Abdelouahed Khalil
Medicine, University of Sherbrooke, Sherbrooke, Quebec J1H 4C4
Corresponding Author: abdelouahed.khalil{at}USherbrooke.ca
Our aim of this study was to investigate the effect of aging on the capacity of high-density lipoproteins (HDL) to promote reverse cholesterol transport (RCT). HDL were isolated from plasma of young (Y-HDL) and elderly (E-HDL) subjects. HDL-mediated cholesterol efflux was studied using THP1 and J774 macrophages. Our results show that E-HDL present a lower capacity to promote cholesterol efflux than Y-HDL (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 the ABCA-1-mediated cholesterol efflux is the more affected pathway in the cholesterol removing capacity. Interestingly, the composition and structure of HDL revealed a reduction in the phosphatidylcholine/sphingomyelin (PC/SPM) ratio (E-HDL: 32.7 ± 2.7 vs. Y-HDL: 40.0 ± 1.9 vs. p = 0.029) and in the phospholipidic-layer membrane fluidity in E-HDL as compared to Y-HDL as well as an alteration in the apoA-I structure and charge. In conclusion, our results shown that elderly-derived HDL present a reduced capacity to promote cholesterol efflux, principally through the ABCA-1 pathway, and this may explain the increase of the incidence of cardiovascular diseases observed during aging.
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