Berrougui Hicham, Isabelle Maxim, Cloutier Martin, Grenier Guillaume, Khalil Abdelouahed
Research Centre on Aging, Orthopaedic Service, University of Sherbrooke, Sherbrooke, Québec, Canada.
J Lipid Res. 2007 Feb;48(2):328-36. doi: 10.1194/jlr.M600167-JLR200. Epub 2006 Nov 8.
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.
我们这项研究的目的是调查衰老对高密度脂蛋白（HDL）促进胆固醇逆向转运能力的影响。从年轻受试者（Y-HDL）和老年受试者（E-HDL）的血浆中分离出HDL。使用THP-1和J774巨噬细胞研究HDL介导的胆固醇流出。我们的结果显示，E-HDL促进胆固醇流出的能力低于Y-HDL（分别为41.7±1.4%对49.0±2.2%；P = 0.013）。随着衰老，HDL介导的胆固醇流出能力的降低在HDL(3)中比在HDL(2)中更显著（Y-HDL(3)，57.3±1%对E-HDL(3)，50.9±2%；P = 0.012）。此外，我们的结果表明，就胆固醇清除能力而言，ABCA1介导的胆固醇流出是受影响更大的途径。有趣的是，HDL的组成和结构显示，与Y-HDL相比，E-HDL的磷脂酰胆碱-鞘磷脂比率降低（E-HDL为32.7±2.7，Y-HDL为40.0±1.9；P = 0.029），E-HDL的磷脂层膜流动性降低，以及载脂蛋白A-I的结构和电荷发生改变。总之，我们的结果表明，E-HDL促进胆固醇流出的能力降低，主要是通过ABCA1途径，这可能解释了在衰老过程中观察到的心血管疾病发病率增加的现象。
