Functional genomics of the human high-density lipoprotein receptor scavenger receptor BI: an old dog with new tricks.
Functional genomics of the human high-density lipoprotein receptor scavenger receptor BI: an old dog with new tricks.
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DOI：
10.1097/med.0b013e32835ed575
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Sahoo D
中科院分区：
文献类型：
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作者：
Chadwick AC;Sahoo D
清道夫受体BI（SR-BI）的动脉粥样硬化保护作用主要归因于其在胆固醇逆向转运（RCT）过程中选择性地将胆固醇酯从高密度脂蛋白（HDL）转移到肝脏的能力。在这篇综述中，我们强调了最近的研究结果，揭示了SR-BI对人类血脂水平和心血管疾病的影响。此外，SR-BI在调节肾上腺和血小板功能，以及人类女性生育能力的额外责任，进行了讨论。在高HDL-胆固醇水平的患者中鉴定了P297 S-、S112 F-和T175 A-突变SR-BI受体的杂合子携带者。来自P297 S-SR-BI载体的HDL不能介导巨噬细胞胆固醇流出，而表达P297 S-SR-BI的肝细胞不能介导HDL-胆固醇酯的选择性摄取。S112 F和T175 A突变型受体在体外表现出相似的胆固醇转运功能受损。P297 S携带者SR-BI功能降低也与类固醇生成减少和血小板功能改变有关。此外，人群研究确定了与女性不孕症相关的SCARB 1变体。SR-BI变体的鉴定证实了该受体在影响人类脂质水平和RCT中的关键作用。在探索旨在降低心血管风险的HDL升高疗法时，需要更深入地了解SR-BI对类固醇生成、血小板功能和生育力的作用。
The athero-protective role of scavenger receptor BI (SR-BI) is primarily attributed to its ability to selectively transfer cholesteryl esters from high density lipoproteins (HDL) to the liver during reverse cholesterol transport (RCT). In this review, we highlight recent findings that reveal the impact of SR-BI on lipid levels and cardiovascular disease in humans. Moreover, additional responsibilities of SR-BI in modulating adrenal and platelet function, as well as female fertility in humans, are discussed. Heterozygote carriers of P297S-, S112F- and T175A- mutant SR-BI receptors were identified in patients with high HDL-cholesterol levels. HDL from P297S-SR-BI carriers was unable to mediate macrophage cholesterol efflux, while hepatocytes expressing P297S-SR-BI were unable to mediate the selective uptake of HDL-cholesteryl esters. S112F- and T175A-mutant receptors exhibited similar impaired cholesterol transport functions in vitro. Reduced SR-BI function in P297S carriers was also associated with decreased steroidogenesis and altered platelet function. Further, human population studies identified SCARB1 variants associated with female infertility. Identification of SR-BI variants confirms the key role of this receptor in influencing lipid levels and RCT in humans. Deeper understanding of the contributions of SR-BI to steroidogenesis, platelet function and fertility is required in light of exploration of HDL-raising therapies aimed at reducing cardiovascular risk.