Rediscovering scavenger receptor type BI: surprising new roles for the HDL receptor.
Rediscovering scavenger receptor type BI: surprising new roles for the HDL receptor.
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DOI：
10.1097/mol.0000000000000413
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发表时间：
2017-06
影响因子：
4.4
通讯作者：
Sorci-Thomas M
中科院分区：
文献类型：
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作者：
Hoekstra M;Sorci-Thomas M
清道夫受体BI （SR-BI）因其在抗动脉粥样硬化逆向胆固醇转运中的作用而闻名，因为它选择性地从高密度脂蛋白（HDL）中吸收胆固醇酯。在这里，我们重点介绍了最近的文献，描述了SR-BI在生理和疾病中的新功能。一项基于大型人群的研究显示，P376L型SR-BI杂合的受试者血浆hdl -胆固醇水平显著升高，心血管疾病的风险增加，这表明人类SR-BI是心血管疾病的重要决定因素。此外，SR-BI已被证明可以调节对lps诱导的组织损伤的易感性和磷酸鞘氨醇1与其受体相互作用的能力，将SR-BI与炎症调节联系起来。此外，分子内的重要结构域（Trp-415）以及SR-BI选择性摄取功能的新调节因子（ppc2）最近已被确定。此外，在多种癌症组织中观察到SR-BI蛋白的相对高表达水平，这与总体生存率降低有关。高密度脂蛋白受体SR-BI是一个潜在的治疗靶点，不仅在心血管疾病设置，而且在炎症条件和癌症。
Scavenger receptor BI (SR-BI) is classically known for its role in anti-atherogenic reverse cholesterol transport as it selectively takes up cholesterol esters from high-density lipoprotein (HDL). Here we have highlighted recent literature that describes novel functions for SR-BI in physiology and disease. A large population based study has revealed that subjects heterozygous for the P376L mutant form of SR-BI showed significantly increased levels of plasma HDL-cholesterol and had increased risk of cardiovascular disease, demonstrating that SR-BI in humans is a significant determinant of cardiovascular disease. Furthermore, SR-BI has been shown to modulate the susceptibility to LPS-induced tissue injury and the ability of sphingosine 1 phosphate to interact with its receptor, linking SR-BI to the regulation of inflammation. In addition, important domains within the molecule (Trp-415) as well as novel regulators (PCEP2) of SR-BI’s selective uptake function have recently been identified. Moreover, relatively high expression levels of the SR-BI protein have been observed in a variety of cancer tissues which is associated with a reduced overall survival rate. The HDL receptor SR-BI is a potential therapeutic target not only in the cardiovascular disease setting, but also in inflammatory conditions as well as in cancer.