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首页> 外文期刊>Current opinion in lipidology >ATP-binding cassette transporter A1 and cholesterol trafficking.
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ATP-binding cassette transporter A1 and cholesterol trafficking.

机译：ATP结合盒转运蛋白A1和胆固醇运输。

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摘要

PURPOSE OF REVIEW: 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 named ATP-binding cassette transporter A1 (ABCA1) mediates secretion of excess cholesterol from cells into the HDL metabolic pathway. The discovery of ABCA1 in 1999 triggered a deluge of studies conducted to characterize the properties of this important transporter. The present review summarizes the more recent of those studies and evaluates their implications for the role of ABCA1 in cholesterol transport, HDL metabolism, and atherogenesis. RECENT FINDINGS: Cell culture experiments have shown that ABCA1 transports cholesterol, phospholipids, and other lipophilic molecules across the plasma membrane, where they are picked up by apolipoproteins containing little or no lipids, but the mechanisms involved are still unclear. It is now apparent that factors in addition to sterols modulate ABCA1 expression by diverse transcriptional and post-transcriptional processes. Studies in humans and mice with ABCA1 mutations revealed that the relative activity of ABCA1 determines plasma HDL levels and influences susceptibility to cardiovascular disease. Mouse models are beginning to provide insights into the function of ABCA1 in vivo but are also raising new questions regarding the contribution of ABCA1 to total cholesterol flux. SUMMARY: Recent studies underscore the critical role of ABCA1 in clearing excess cholesterol from macrophages and generating HDL particles, implicating ABCA1 as an attractive new therapeutic target for treating cardiovascular disease.
机译：审查的目的：心血管疾病的两个标志是动脉壁中存在富含固醇的巨噬细胞和血浆HDL水平降低。一种称为ATP结合盒转运蛋白A1（ABCA1）的细胞膜蛋白介导细胞中多余胆固醇的分泌进入HDL代谢途径。 1999年ABCA1的发现引发了大量的研究，以表征这种重要转运蛋白的特性。本综述总结了这些研究中的最新成果，并评估了它们对ABCA1在胆固醇转运，HDL代谢和动脉粥样硬化中的作用的影响。最近的发现：细胞培养实验表明，ABCA1通过质膜转运胆固醇，磷脂和其他亲脂性分子，在那里它们被几乎不含脂质或不含脂质的载脂蛋白所吸收，但所涉及的机制仍不清楚。现在很明显，除固醇外，其他因素还通过多种转录和转录后过程调节ABCA1表达。对具有ABCA1突变的人和小鼠的研究表明，ABCA1的相对活性决定了血浆HDL水平并影响了对心血管疾病的敏感性。小鼠模型开始提供有关ABCA1体内功能的见解，但也引发了有关ABCA1对总胆固醇通量的贡献的新问题。简介：最近的研究强调了ABCA1在清除巨噬细胞中多余的胆固醇并产生HDL颗粒方面的关键作用，这暗示ABCA1是治疗心血管疾病的有吸引力的新治疗靶标。

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