ABCG5/ABCG8 固醇转运蛋白与植物甾醇：对心脏代谢疾病的影响
The ABCG5 ABCG8 sterol transporter and phytosterols: implications for cardiometabolic disease.
作者信息
Sabeva Nadezhda S, Liu Jingjing, Graf Gregory A
机构信息
University of Kentucky, College of Pharmacy, Pharmaceutical Sciences, Lexington, KY 40536-0082, USA.
出版信息
Curr Opin Endocrinol Diabetes Obes. 2009 Apr;16(2):172-7. doi: 10.1097/med.0b013e3283292312.
PURPOSE OF REVIEW
This review summarizes recent developments in the activity, regulation, and physiology of the ABCG5 ABCG8 (G5G8) transporter and the use of its xenobiotic substrates, phytosterols, as cholesterol lowering agents in the treatment of cardiovascular disease. Recent progress has significant implications for the role of G5G8 and its substrates in complications associated with features of the metabolic syndrome.
RECENT FINDINGS
Recent reports expand the clinical presentation of sitosterolemia to include platelet and adrenal dysfunction. The G5G8 sterol transporter is critical to hepatobiliary excretion of cholesterol under nonpathological conditions and has been linked to the cholesterol gallstone susceptibility. Finally, the cardiovascular benefits of cholesterol lowering through the use of phytosterol supplements were offset by vascular dysfunction, suggesting that alternative strategies to reduced cholesterol absorption offer greater benefit.
SUMMARY
Insulin resistance elevates G5G8 and increases susceptibility to cholesterol gallstones. However, this transporter is critical for the exclusion of phytosterols from the absorptive pathways in the intestine. Challenging the limits of this protective mechanism through phytosterol supplementation diminishes the cardioprotective benefits of cholesterol lowering in mouse models of cardiovascular disease.
综述目的
本综述总结了ABCG5 ABCG8（G5G8）转运蛋白在活性、调节和生理学方面的最新进展，以及其外源性底物植物甾醇作为降胆固醇药物在治疗心血管疾病中的应用。最近的进展对G5G8及其底物在与代谢综合征特征相关的并发症中的作用具有重要意义。
最新发现
最近的报告将谷甾醇血症的临床表现扩展至包括血小板和肾上腺功能障碍。G5G8甾醇转运蛋白在非病理条件下对肝胆系统排泄胆固醇至关重要，并且与胆固醇胆结石易感性有关。最后，通过使用植物甾醇补充剂降低胆固醇带来的心血管益处被血管功能障碍抵消，这表明降低胆固醇吸收的替代策略可能带来更大益处。
总结
胰岛素抵抗会提高G5G8水平，并增加患胆固醇胆结石的易感性。然而，这种转运蛋白对于将植物甾醇排除在肠道吸收途径之外至关重要。在心血管疾病小鼠模型中，通过补充植物甾醇来挑战这种保护机制的极限，会削弱降低胆固醇带来的心脏保护益处。
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