Wihuri Research Institute, Helsinki, Finland.
Prog Lipid Res. 2013 Jul;52(3):317-28. doi: 10.1016/j.plipres.2013.04.003. Epub 2013 Apr 20.
In the arterial intima, macrophages become cholesterol-enriched foam cells and atherosclerotic lesions are generated. This atherogenic process can be attenuated, prevented, or even reversed by HDL particles capable of initiating a multistep pathway known as the macrophage-specific reverse cholesterol transport. The macrophage-derived cholesterol released to HDL is taken up by the liver, secreted into the bile, and ultimately excreted in the feces. Importantly, the absorptive epithelial cells lining the lumen of the small intestine, the enterocytes, express several membrane-associated proteins which mediate the influx of luminal cholesterol and its subsequent efflux at their apical and basolateral sides. Moreover, generation of intestinal HDL and systemic effects of the gut microbiota recently revealed a direct link between the gut and the cholesterol cargo of peripheral macrophages. This review summarizes experimental evidence establishing that the reverse cholesterol transport pathway which initiates in macrophages is susceptible to modulation in the small intestine. We also describe four paths which govern cholesterol passage across the enterocyte and define a role for the gut in the regulation of reverse cholesterol transport. Understanding the concerted function of these paths may be useful when designing therapeutic strategies aimed at removing cholesterol from the foam cells which occupy atherosclerotic lesions.
在动脉内膜中，巨噬细胞变成富含胆固醇的泡沫细胞，形成动脉粥样硬化病变。载脂蛋白 HDL 颗粒能够启动一个多步骤的途径，称为巨噬细胞特异性胆固醇逆转运，从而减轻、预防甚至逆转这种动脉粥样硬化形成过程。巨噬细胞释放到 HDL 的胆固醇被肝脏摄取，分泌到胆汁中，最终从粪便中排出。重要的是，小肠腔的吸收上皮细胞，即肠细胞，表达几种膜相关蛋白，这些蛋白介导腔内胆固醇的内流及其随后在其顶端和基底外侧的流出。此外，肠道内 HDL 的生成和肠道微生物群的全身作用最近揭示了肠道与外周巨噬细胞胆固醇货物之间的直接联系。这篇综述总结了实验证据，证明起始于巨噬细胞的胆固醇逆转运途径易受小肠调节。我们还描述了控制胆固醇穿过肠细胞的四条途径，并定义了肠道在胆固醇逆转运调节中的作用。了解这些途径的协同作用可能有助于设计旨在从占据动脉粥样硬化病变的泡沫细胞中去除胆固醇的治疗策略。
