Direct evidence in vivo of impaired macrophage-specific reverse cholesterol transport in ATP-binding cassette transporter A1-deficient mice

被引:31
作者
Calpe-Berdiel, L
Rotllan, N
Palomer, X
Ribas, V
Blanco-Vaca, F
Escolà-Gil, JC
机构
[1] Hosp Santa Creu & Sant Pau, Serv Bioquim, Barcelona 08025, Spain
[2] Hosp Santa Creu & Sant Pau, Inst Recerca, Barcelona 08025, Spain
[3] Hosp Santa Creu & Sant Pau, Serv Endocrinol, Barcelona 08025, Spain
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 2005年 / 1738卷 / 1-3期
关键词
ATP-binding cassette transporter A1; high-density lipoprotein; macrophage; reverse cholesterol transport;
D O I
10.1016/j.bbalip.2005.11.012
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
The ATP-binding cassette transporter A1 (ABCA1) is a key regulator of high-density lipoprotein (HDL) metabolism. There is strong evidence that ABCA1 is a key regulator of reverse cholesterol transport (RCT). However, this could not be proved in vivo since hepatobiliary cholesterol transport was unchanged in ABCA1-deficient mice (ABCA1-/-). We used ABCA1-/- mice to test the hypothesis that ABCA1 is a critical determinant of macrophage-specific RCT. Although this cell-specific RCT only accounts for a tiny part of total RCT, it is widely accepted that it may have a major impact on atherosclerosis susceptibility. [H-3]cholesterol-labeled endogenous macrophages were injected intraperitoneally into wild-type ABCA1+/+, ABCA1+/- and ABCA1-/- mice maintained on a chow diet. A direct relationship was observed between ABCA1 gene dose and plasma [H-3]cholesterol at 24 and 48 h after the injection of tracer into the mice. Forty-eight hours after this injection, ABCA1-/- mice had significantly reduced [H-3]cholesterol in liver (2.8-fold), small intestine enterocytes (1.7-fold) and feces (2-fold). To our knowledge, this is the first direct in vivo quantitative evidence that ABCA1 is a critical determinant of macrophage-specific RCT. (c) 2005 Elsevier B.V All rights reserved.
引用
收藏
页码:6 / 9
页数:4
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