New developments in selective cholesteryl ester uptake.
New developments in selective cholesteryl ester uptake.
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DOI：
10.1097/mol.0b013e3283638042
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发表时间：
2013-10
影响因子：
4.4
通讯作者：
van der Westhuyzen DR
中科院分区：
文献类型：
--
作者：
Meyer JM;Graf GA;van der Westhuyzen DR
已知选择性脂质摄取（SLU）是实验动物和人类脂蛋白胆固醇代谢的主要途径，但仍知之甚少。本文综述了由HDL受体清道夫受体B型I（SR-BI）介导的SLU，并强调了与SLU途径在胆固醇稳态中的影响有关的几个令人惊讶的新发现。在某些条件下，SR-BI介导的SLU独立于ABCG 5/G8介导的胆汁胆固醇分泌而促进胆固醇逆向转运（RCT），这意味着一种新的转运机制。糖尿病小鼠肝脏SR-BI表达和RCT降低。法尼醇X受体（FXR）和微小RNA miR-185、miR-96和miR-223是用于增加SR-BI表达的新兴治疗靶标。不依赖SR-BI的选择性胆固醇酯摄取是巨噬细胞泡沫细胞的一种新的特征性途径。新的发现强调了SR-BI介导的SLU在肝脏SLU和RCT中的重要性，同时表明需要进一步研究来定义SLU途径，包括SR-BI非依赖性巨噬细胞选择性胆固醇酯摄取。这些途径中胆固醇的细胞内运输似乎对其正常功能至关重要，并且是正在进行的研究的主要课题。
Selective lipid uptake (SLU) is known to be a major pathway of lipoprotein cholesterol metabolism in experimental animals and humans, but remains poorly understood. This review provides a brief overview of SLU mediated by the HDL receptor scavenger receptor B-type I (SR-BI), and highlights several surprising new findings related to the impact of SLU pathways in cholesterol homeostasis. Under certain conditions, SR-BI-mediated SLU contributes to reverse cholesterol transport (RCT) independently of ABCG5/G8-mediated biliary cholesterol secretion, implying a novel trafficking mechanism. Hepatic SR-BI expression and RCT are decreased in diabetic mice. Farnesoid X receptor (FXR) and the microRNAs miR-185, miR-96 and miR-223 are emerging therapeutic targets for increasing SR-BI expression. SR-BI-independent selective cholesteryl ester uptake is a newly characterized pathway in macrophage foam cells. New findings underscore the importance of SR-BI-mediated SLU in hepatic SLU and RCT, while indicating that further investigation is needed to define SLU pathways, including SR-BI-independent macrophage selective cholesteryl ester uptake. The intracellular trafficking of cholesterol in these pathways appears to be critical to their normal function and is a major subject of ongoing studies.