期刊
PROGRESS IN LIPID RESEARCH
卷 52, 期 3, 页码 317-328出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.plipres.2013.04.003
关键词
Atherosclerosis; Cholesterol absorption; Enterocyte; Intestinal cholesterol transporters; Macrophage; Reverse cholesterol transport
资金
- European Cooperation in Science and Technology (COST) action [BM0904]
- Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III [FIS 11-0176, FIS 12-00291]
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. (C) 2013 Elsevier Ltd. All rights reserved.
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