title: Ecto-F1-ATPase/P2Y pathways in metabolic and vascular functions of high density lipoproteins.
abstract: The atheroprotective property of High Density Lipoprotein (HDL) is supported by many epidemiological studies and cellular and in vivo approaches on animal models. While the anti-atherogenic effects of HDL are thought to derive primarily from its role in reverse cholesterol transport, together with anti-inflammatory, anti-oxidant, anti-thrombotic and cytoprotective properties, the mechanisms that support these effects are still not completely understood. However, many advances in identifying the cellular partners involved in HDL functions have been made over the last two decades. This review highlights the diverse roles of the HDL receptor ecto-F1-ATPase coupled to purinergic P2Y receptors in the modulation of important metabolic and vascular functions of HDL. On hepatocytes, the ecto-F1-ATPase is coupled to P2Y13 receptor and contributes to HDL holoparticle endocytosis. On endothelial cells, ecto-F1-ATPase/P2Ys pathway is involved in HDL-mediated endothelial protection and HDL transcytosis. The clinical relevance of this F1-ATPase/P2Ys axis in humans has recently been supported by the identification of serum F1-ATPase inhibitor (IF1) as an independent determinant of HDL-Cholesterol (HDL-C) and coronary heart disease risk. Therapeutic strategies targeting F1-ATPase/P2Y pathways for the treatment of atherosclerosis are currently being explored.
authors.affiliation: INSERM, UMR 1048, Institut des Maladies Métaboliques et Cardiovasculaires de Toulouse, Toulouse, France; Université de Toulouse III, UMR 1048, Toulouse, France; CHU Toulouse, Department of Biochemistry, Toulouse, France. Electronic address: laurent.martinez@inserm.fr.
authors.forename: Laurent O
authors.initials: LO
authors.lastname: Martinez
authors.affiliation: INSERM, UMR 1048, Institut des Maladies Métaboliques et Cardiovasculaires de Toulouse, Toulouse, France; Université de Toulouse III, UMR 1048, Toulouse, France.
authors.forename: Souad
authors.initials: S
authors.lastname: Najib
authors.affiliation: INSERM, UMR 1048, Institut des Maladies Métaboliques et Cardiovasculaires de Toulouse, Toulouse, France; Université de Toulouse III, UMR 1048, Toulouse, France; CHU Toulouse, Department of Biochemistry, Toulouse, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Perret
authors.affiliation: INSERM, UMR 1048, Institut des Maladies Métaboliques et Cardiovasculaires de Toulouse, Toulouse, France; Université de Toulouse III, UMR 1048, Toulouse, France; Faculté de Pharmacie, Chemin des Maraichers, Toulouse, France.
authors.forename: Cendrine
authors.initials: C
authors.lastname: Cabou
authors.affiliation: INSERM, UMR 1048, Institut des Maladies Métaboliques et Cardiovasculaires de Toulouse, Toulouse, France; Université de Toulouse III, UMR 1048, Toulouse, France.
authors.forename: Laeticia
authors.initials: L
authors.lastname: Lichtenstein
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002470:Cell Survival; D002784:Cholesterol / Q000737:chemistry; D008076:Cholesterol, HDL / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism; D004705:Endocytosis; D042783:Endothelial Cells / Q000166:cytology; D004791:Enzyme Inhibitors / Q000737:chemistry; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D058470:Receptors, Purinergic P2Y / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D001647:Bile Acids and Salts; D008076:Cholesterol, HDL; D004791:Enzyme Inhibitors; D008075:Lipoproteins, HDL; D058470:Receptors, Purinergic P2Y; D002784:Cholesterol; D000251:Adenosine Triphosphatases; C027201:ectoATPase
keywords: ATP synthase; Apolipoprotein A-I; Bile acids; Endothelial protection; High density lipoprotein; Purinergic receptor