Study of ABCA1 function in transgenic mice
Study of ABCA1 function in transgenic mice
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DOI：
10.1161/01.atv.0000055194.85073.ff
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发表时间：
2003-06-01
影响因子：
8.7
通讯作者：
Santamarina-Fojo, S
中科院分区：
文献类型：
--
作者：
Joyce, C;Freeman, L;Santamarina-Fojo, S
ATP结合盒转运蛋白A1（ABCA 1），在1999年被鉴定为丹吉尔病的基因缺陷，促进细胞胆固醇从巨噬细胞和其他外周组织流出到载脂蛋白受体。这些ABCA 1介导的过程预计具有抗动脉粥样硬化特性，促进了增加ABCA 1基因表达的药理学试剂的开发以及ABCA 1转基因小鼠系的建立。ABCA 1-Tg小鼠的初步研究似乎验证了选择这种转运蛋白作为治疗低HDL综合征和心血管疾病的治疗靶点，但也提出了关于ABCA 1功能的新问题。特别是，肝脏和外周ABCA 1对血浆HDL水平和逆转胆固醇转运的相对贡献，以及ABCA 1在调节含载脂蛋白B的脂蛋白的血浆浓度和预防动脉粥样硬化中的潜在作用，似乎是有前途的研究领域。本综述总结了最新的研究，并讨论了这些转基因小鼠模型提供的见解。
The ATP-binding cassette transporter A1 (ABCA1), identified in 1999 as the gene defective in Tangier disease, promotes efflux of cellular cholesterol from macrophages and other peripheral tissues to apolipoprotein acceptors. These ABCA1-mediated processes are anticipated to have antiatherogenic properties, prompting the development of pharmacological agents that increase ABCA1 gene expression as well as the establishment of ABCA1-transgenic mouse lines. Preliminary studies of ABCA1-Tg mice seem to validate the selection of this transporter as a therapeutic target for the treatment of low HDL syndromes and cardiovascular disease but have also raised new questions regarding the function of ABCA1. In particular, the relative contribution of hepatic and peripheral ABCA1 to plasma HDL levels and to reverse cholesterol transport, as well as the potential role of ABCA1 in modulating the plasma concentrations of the apolipoprotein B-containing lipoproteins and protecting against atherosclerosis, seem to be promising areas of investigation. The present review summarizes the most recent studies and discusses insights provided by these transgenic mouse models.