Division of Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, USA.
Curr Opin Lipidol. 2012 Oct;23(5):487-93. doi: 10.1097/MOL.0b013e328357ba61.
This review highlights the diverse roles of the high-affinity HDL receptor scavenger receptor class B, type I (SR-BI) in the modulation of global cholesterol homeostasis and vascular cell function, and the potential implications of these processes in atherosclerosis.
SR-BI in the liver plays a critical role in reverse cholesterol transport and it dramatically impacts the characteristics of the HDL particle, and through reverse cholesterol transport it promotes an antiatherogenic lipid environment in the vascular wall. SR-BI in macrophages may influence their inflammatory phenotype. In endothelial cells, SR-BI mediates HDL-induced endothelial nitric oxide synthase activation and proliferation and migration, and in platelets SR-BI may be prothrombotic in the setting of dyslipidemia. Several polymorphisms of SR-BI have been reported in humans that influence receptor expression or function.
In addition to regulating global lipid metabolism, SR-BI influences the functions of a variety of vascular cells relevant to atherosclerosis. Studies of SR-BI genetics in humans partially support the conclusions drawn from experimental models. However, because of the multiple functions of SR-BI, the diversity of cell types in which it is expressed, and the influence of the receptor on the characteristics of its own ligand, our understanding of the biology of the receptor is just emerging.
本文重点介绍高亲和力 HDL 受体清道夫受体 B 型,I 类(SR-BI)在调节全身胆固醇稳态和血管细胞功能方面的多种作用,以及这些过程在动脉粥样硬化中的潜在意义。
肝脏中的 SR-BI 在胆固醇逆转运中发挥关键作用,它显著影响 HDL 颗粒的特征,并通过胆固醇逆转运促进血管壁中的抗动脉粥样硬化脂质环境。巨噬细胞中的 SR-BI 可能影响其炎症表型。在内皮细胞中,SR-BI 介导 HDL 诱导的内皮型一氧化氮合酶激活和增殖及迁移,而在血小板中,SR-BI 在血脂异常时可能具有促血栓形成作用。已经在人类中报道了几种影响受体表达或功能的 SR-BI 多态性。
除了调节全身脂质代谢外,SR-BI 还影响与动脉粥样硬化相关的多种血管细胞的功能。人类对 SR-BI 遗传学的研究部分支持了从实验模型中得出的结论。然而,由于 SR-BI 的多种功能、其表达的细胞类型的多样性以及受体对其自身配体特征的影响,我们对受体生物学的理解才刚刚开始。