Molecular basis of cholesterol homeostasis: lessons from Tangier disease and ABCA1

被引:70
作者
Oram, JF [1 ]
机构
[1] Univ Washington, Dept Med, Seattle, WA 98195 USA
关键词
D O I
10.1016/S1471-4914(02)02289-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
High-density lipoproteins (HDLs) play a role in transporting cholesterol from peripheral tissues to the liver for elimination from the body. Two hallmarks of cardiovascular disease are the presence of sterol-laden macrophages in the artery wall and reduced plasma HDL levels. A cell-membrane protein called ABCA1 mediates the secretion of excess cholesterol from cells into the HDL metabolic pathway. Mutations in ABCA 1 cause Tangier disease, a severe HDL deficiency syndrome characterized by accumulation of cholesterol in tissue macrophages and prevalent atherosclerosis. Because of its ability to deplete macrophages of cholesterol and to raise plasma HDL levels, ABCA1 has become a promising therapeutic target for preventing cardiovascular disease.
引用
收藏
页码:168 / 173
页数:6
相关论文
共 72 条
[1]   Effect of up-regulating individual steps in the reverse cholesterol transport pathway on reverse cholesterol transport in normolipidemic mice [J].
Alam, K ;
Meidell, RS ;
Spady, DK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (19) :15641-15649
[2]   The caveolae membrane system [J].
Anderson, RGW .
ANNUAL REVIEW OF BIOCHEMISTRY, 1998, 67 :199-225
[3]  
Assmann G, 1995, METABOLIC MOL BASES, P2053
[4]  
Attie AD, 2000, CIRCULATION, V102, P312
[5]   Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters [J].
Berge, KE ;
Tian, H ;
Graf, GA ;
Yu, LQ ;
Grishin, NV ;
Schultz, J ;
Kwiterovich, P ;
Shan, B ;
Barnes, R ;
Hobbs, HH .
SCIENCE, 2000, 290 (5497) :1771-1775
[6]   The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease [J].
Bodzioch, M ;
Orsó, E ;
Klucken, T ;
Langmann, T ;
Böttcher, L ;
Diederich, W ;
Drobnik, W ;
Barlage, S ;
Büchler, C ;
Porsch-Özcürümez, M ;
Kaminski, WE ;
Hahmann, HW ;
Oette, K ;
Rothe, G ;
Aslanidis, C ;
Lackner, KJ ;
Schmitz, G .
NATURE GENETICS, 1999, 22 (04) :347-351
[7]   The correlation of ATP-binding cassette 1 mRNA levels with cholesterol efflux from various cell lines [J].
Bortnick, AE ;
Rothblat, GH ;
Stoudt, G ;
Hoppe, KL ;
Royer, LJ ;
McNeish, J ;
Francone, OL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (37) :28634-28640
[8]   Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency [J].
Brooks-Wilson, A ;
Marcil, M ;
Clee, SM ;
Zhang, LH ;
Roomp, K ;
van Dam, M ;
Yu, L ;
Brewer, C ;
Collins, JA ;
Molhuizen, HOF ;
Loubser, O ;
Ouelette, BFF ;
Fichter, K ;
Ashbourne-Excoffon, KJD ;
Sensen, CW ;
Scherer, S ;
Mott, S ;
Denis, M ;
Martindale, D ;
Frohlich, J ;
Morgan, K ;
Koop, B ;
Pimstone, S ;
Kastelein, JJP ;
Genest, J ;
Hayden, MR .
NATURE GENETICS, 1999, 22 (04) :336-345
[9]  
Brousseau ME, 2000, J LIPID RES, V41, P1125
[10]   A RECEPTOR-MEDIATED PATHWAY FOR CHOLESTEROL HOMEOSTASIS [J].
BROWN, MS ;
GOLDSTEIN, JL .
SCIENCE, 1986, 232 (4746) :34-47