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

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• 作者：Laura Calpe-Berdiel ; Noemi Rotllan ; Xavier Palomer ; Vicent Ribas ; Francisco Blanco-Vaca and Joan Carles Escolà ; -Gil
• 关键词：ATP-binding cassette transporter A1 ; High-density lipoprotein ; Macrophage ; Reverse cholesterol transport
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2005
• 出版时间：30 December 2005
• 年：2005
• 卷：1738
• 期：1-3
• 页码：6-9
• 全文大小：127 K

文摘

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. [³H]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 [³H]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 [³H]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.