The role of the gut in reverse cholesterol transport--focus on the enterocyte

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.