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首页> 外文期刊>Biochimica et Biophysica Acta. Molecular and cell biology of Lipids >Direct evidence in vivo of impaired macrophage-specific reverse cholesterol transport in ATP-binding cassette transporter A1-deficient mice
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Direct evidence in vivo of impaired macrophage-specific reverse cholesterol transport in ATP-binding cassette transporter A1-deficient mice

机译：ATP结合盒转运蛋白A1缺陷小鼠中巨噬细胞特异性逆胆固醇转运受损的体内直接证据

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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.
机译：ATP结合盒转运蛋白A1（ABCA1）是高密度脂蛋白（HDL）代谢的关键调节剂。有充分的证据表明ABCA1是胆固醇逆向转运（RCT）的关键调节剂。但是，这不能在体内得到证实，因为在ABCA1缺陷型小鼠（ABCA1-/-）中肝胆胆固醇的转运没有改变。我们使用ABCA1-/-小鼠测试了ABCA1是巨噬细胞特异性RCT的关键决定因素的假设。尽管该细胞特异性RCT仅占总RCT的一小部分，但它被广泛接受可能对动脉粥样硬化易感性产生重大影响。将[H-3]胆固醇标记的内源性巨噬细胞腹膜内注射到维持饮食的野生型ABCA1 + / +，ABCA1 +/-和ABCA1-/-小鼠中。在向小鼠注射示踪剂后24和48小时，观察到ABCA1基因剂量与血浆[H-3]胆固醇之间存在直接关系。注射后48小时，ABCA1-/-小鼠肝脏中的[H-3]胆固醇显着降低（2.8倍），小肠肠上皮细胞（1.7倍）和粪便（2倍）减少。据我们所知，这是第一个直接的体内定量证据，表明ABCA1是巨噬细胞特异性RCT的关键决定因素。 （c）2005 Elsevier B.V保留所有权利。

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