Age-Associated Decrease of High-Density Lipoprotein-Mediated Reverse Cholesterol Transport Activity

被引:37
作者
Berrougui, Hicham [1 ,2 ]
Khalil, Abdelouahed [1 ,2 ]
机构
[1] Univ Sherbrooke, Res Ctr Aging, Geriatr Inst, Sherbrooke, PQ J1H 4C4, Canada
[2] Univ Sherbrooke, Dept Med, Geriatr Serv, Sherbrooke, PQ J1H 4C4, Canada
基金
加拿大健康研究院;
关键词
APOLIPOPROTEIN-A-I; SCAVENGER RECEPTOR BI; SELECTIVE LIPID UPTAKE; CELLULAR CHOLESTEROL; PARAOXONASE ACTIVITY; SR-BI; SERUM PARAOXONASE; GAMMA-RADIOLYSIS; INCREASED SUSCEPTIBILITY; ATHEROSCLEROTIC LESIONS;
D O I
10.1089/rej.2008.0840
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
High-density lipoproteins (HDL) are considered atheroprotective in contrast to low-density lipoproteins (LDL), which are atherogenic in their oxidized form. A growing body of evidence suggests that HDL exert part of their antiatherogenic effect by counteracting LDL oxidation as well as their proinflammatory effect. However, a number of studies, carried over the past 30 years, have shown that cholesterol efflux plays a major role in the atheroprotective effects of HDL and cholesterol homeostasis. These studies have further identified the scavenger receptor type B-I (SR-BI), the adenosine triphosphate (ATP)-binding cassette transporters ATP-binding cassette subfamily A1 (ABCA1), ATP-binding cassette subfamily G1 (ABCG1) and ABCG4, the liver X receptor/retinoid X receptor (LXR/RXR) and peroxisome proliferator-activated receptor gamma (PPAR gamma) transcription factors, the HDL components apolipoprotein A-I (apoA-I), lecithin-cholesterol acyltransferase (LCAT), and phospholipids as additional mediators of cholesterol transport. Cholesterol efflux occurs via three independent pathways: (1) aqueous diffusion, (2) nonspecific efflux via SR-BI receptors, and (3) specific efflux via cholesterol-responsive members of the ABC superfamily. Whereas aqueous diffusion and scavenger receptor class B, type I (SR-BI)-mediated efflux transport free cholesterol to a wide variety of cholesterol acceptors (particles containing phospholipids, HDL, and lipidated apo-lipoproteins; LDL, etc), the ABCA1 pathway mediates the transport of cholesterol in a unidirectional manner, mainly to lipid-poor apoA-I. In contrast, the ABCG1 pathway is responsible for the transport of cholesterol to all the subfamily members of HDL. Although HDL-mediated cholesterol efflux is apoA-I-dependent, recent studies have suggested an involvement of the enzyme paraoxonase 1 (PON1). Cholesterol efflux is carried on by a number of factors such as genetic mutations, smoking, stress, and high-fat diets. It is attenuated with aging due to changes in the composition and structure of HDL, especially the phosphatidylcholine/sphingomyelin ratio, the fluidity of the phospholipidic layer, the concentration of apoA-I, and the activity of PON1. This review summarizes the findings that cholesterol homeostasis is disrupted with aging as a consequence of dysfunctional cholesterol efflux and the impairment of physiological functions.
引用
收藏
页码:117 / 126
页数:10
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