Transintestinal and Biliary Cholesterol Secretion Both Contribute to Macrophage Reverse Cholesterol Transport in RatsBrief Report
Transintestinal and Biliary Cholesterol Secretion Both Contribute to Macrophage Reverse Cholesterol Transport in RatsBrief Report
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DOI：
10.1161/atvbaha.116.308558
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发表时间：
2017-04-01
影响因子：
8.7
通讯作者：
Groen, Albert K.
中科院分区：
文献类型：
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作者：
de Boer, Jan Freark;Schonewille, Marleen;Groen, Albert K.
胆固醇逆向转运包括胆固醇从巨噬细胞流出，随后随粪便从体内排出，从而防止动脉粥样硬化斑块的形成。由于缺乏合适的动物模型，可以评估胆汁胆固醇分泌和经肠胆固醇排泄（TICE）在生理条件下对巨噬细胞逆向胆固醇转运的各自贡献，这两种途径在这一过程中的相对重要性仍然存在争议。连续三天。将每组2只体重匹配的大鼠指定为一对，两只大鼠均在胆管和十二指肠中配备插管。将大鼠1的胆汁转移至大鼠2的十二指肠，而将大鼠2的胆汁改道至大鼠1的十二指肠。接下来，向大鼠1注射负载[H-3]胆固醇的巨噬细胞。[H-3]因此，通过胆汁途径分泌的胆固醇被转移至大鼠2，因此可以从该大鼠的粪便中定量。另一方面，大鼠1粪便中的[H-3]胆固醇示踪剂反映了通过TICE排泄的巨噬细胞源性胆固醇。使用这种设置，我们发现，63%的标签分泌的粪便中性固醇已经通过胆道途径，而37%的排泄通过TICE. Conclusions TICE和胆汁胆固醇分泌有助于巨噬细胞的胆固醇逆向转运在大鼠。然而，大多数巨噬细胞衍生的胆固醇通过肝胆途径排泄。视觉概述-本文提供在线视觉概述。
Objective-Reverse cholesterol transport comprises efflux of cholesterol from macrophages and its subsequent removal from the body with the feces and thereby protects against formation of atherosclerotic plaques. Because of lack of suitable animal models that allow for evaluation of the respective contributions of biliary cholesterol secretion and transintestinal cholesterol excretion (TICE) to macrophage reverse cholesterol transport under physiological conditions, the relative importance of both pathways in this process has remained controversial.Approach and Results-To separate cholesterol traffic via the biliary route from TICE, bile flow was mutually diverted between rats, continuously, for 3 days. Groups of 2 weight-matched rats were designated as a pair, and both rats were equipped with cannulas in the bile duct and duodenum. Bile from rat 1 was diverted to the duodenum of rat 2, whereas bile from rat 2 was rerouted to the duodenum of rat 1. Next, rat 1 was injected with [H-3] cholesterol-loaded macrophages. [H-3] Cholesterol secreted via the biliary route was consequently diverted to rat 2 and could thus be quantified from the feces of that rat. On the other hand, [H-3] cholesterol tracer in the feces of rat 1 reflected macrophage-derived cholesterol excreted via TICE. Using this setup, we found that 63% of the label secreted with the fecal neutral sterols had travelled via the biliary route, whereas 37% was excreted via TICE.Conclusions-TICE and biliary cholesterol secretion contribute to macrophage reverse cholesterol transport in rats. The majority of macrophage-derived cholesterol is however excreted via the hepatobiliary route.Visual Overview-An online visual overview is available for this article.