title: The ABCG5 ABCG8 sterol transporter and phytosterols:  implications for cardiometabolic disease.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Kentucky, College of Pharmacy, Pharmaceutical Sciences, Lexington, KY 40536-0082, USA.
authors.forename: Nadezhda S
authors.initials: NS
authors.lastname: Sabeva
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Graf
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D006331:Heart Diseases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000235:genetics* / Q000378:metabolism*; D008659:Metabolic Diseases / Q000235:genetics* / Q000378:metabolism*; D010840:Phytosterols / Q000378:metabolism*; D013261:Sterols / Q000097:blood
chemical_list: C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D010840:Phytosterols; D013261:Sterols