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The ABCG5 ABCG8 Sterol Transporter and Phytosterols: Implications for Cardiometabolic Disease

Overview
Specialty Endocrinology
Date 2009 Mar 25
PMID 19306529
Citations 17
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Abstract

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.

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References
1.
Awad A, Barta S, Fink C, Bradford P . beta-Sitosterol enhances tamoxifen effectiveness on breast cancer cells by affecting ceramide metabolism. Mol Nutr Food Res. 2008; 52(4):419-26. DOI: 10.1002/mnfr.200700222. View

2.
Plat J, de Jong A, Volger O, Princen H, Mensink R . Preferential campesterol incorporation into various tissues in apolipoprotein E*3-Leiden mice consuming plant sterols or stanols. Metabolism. 2008; 57(9):1241-7. DOI: 10.1016/j.metabol.2008.04.018. View

3.
Groen A, Kunne C, Jongsma G, van den Oever K, Mok K, Petruzzelli M . Abcg5/8 independent biliary cholesterol excretion in Atp8b1-deficient mice. Gastroenterology. 2008; 134(7):2091-100. DOI: 10.1053/j.gastro.2008.02.097. View

4.
Kruit J, Lyndsay Drayer A, Bloks V, Blom N, Olthof S, Sauer P . Plant sterols cause macrothrombocytopenia in a mouse model of sitosterolemia. J Biol Chem. 2007; 283(10):6281-7. DOI: 10.1074/jbc.M706689200. View

5.
van der Veen J, Havinga R, Bloks V, Groen A, Kuipers F . Cholesterol feeding strongly reduces hepatic VLDL-triglyceride production in mice lacking the liver X receptor alpha. J Lipid Res. 2006; 48(2):337-47. DOI: 10.1194/jlr.M600170-JLR200. View