title: Distinct Roles of Apolipoproteins A1 and E in the Modulation of High-Density Lipoprotein Composition and Function.
abstract: In addition to high-density lipoprotein cholesterol (HDL-C) levels, HDL quality also appears to be very important for atheroprotection. Analysis of various clinical paradigms suggests that the lipid and apolipoprotein composition of HDL defines its size, shape, and functions and may determine its beneficial effects on human health. Previously, we reported that like apolipoprotein A-I (Apoa1), apolipoprotein E (Apoe) is also capable of promoting the de novo biogenesis of HDL with the participation of ATP binding cassette A lipid transporter member 1 (Abca1) and plasma enzyme lecithin:cholesterol acyltransferase (Lcat), in a manner independent of a functional Apoa1. Here, we performed a comparative analysis of the functions of these HDL subpopulations. Specifically, Apoe and Apoa1 double-deficient (Apoe(-/-) × Apoa1(-/-)) mice were infected with APOA1- or APOE3-expressing adenoviruses, and APOA1-containing HDL (APOA1-HDL) and APOE3-containing HDL (APOE3-HDL), respectively, were isolated and analyzed by biochemical and physicochemical methods. Western blot and lipidomic analyses indicated significant differences in the apolipoprotein and lipid composition of the two HDL species. Moreover APOE3-HDL presented a markedly reduced antioxidant potential and Abcg1-mediated cholesterol efflux capacity. Surprisingly, APOE3-HDL but not APOA1-HDL attenuated LPS-induced production of TNFα in RAW264.7 cells, suggesting that the anti-inflammatory effects of APOA1 are dependent on APOE expression. Taken together, our data indicate that APOA1 and APOE3 recruit different apolipoproteins and lipids on the HDL particle, leading to structurally and functionally distinct HDL subpopulations. The distinct role of these two apolipoproteins in the modulation of HDL functionality may pave the way toward the development of novel pharmaceuticals that aim to improve HDL functionality.
authors.affiliation: Department of Pharmacology, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors.forename: Serafoula
authors.initials: S
authors.lastname: Filou
authors.affiliation: ICANalytics, ICAN , 83 Bd de l'hopital, 75013 Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lhomme
authors.affiliation: Department of Pharmacology, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors.forename: Eleni A
authors.initials: EA
authors.lastname: Karavia
authors.affiliation: Department of Pharmacology, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Kalogeropoulou
authors.affiliation: Department of Pharmacology, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Theodoropoulos
authors.affiliation: Department of Pharmacology, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Zvintzou
authors.affiliation: Department of Medical Physics, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors.forename: George C
authors.initials: GC
authors.lastname: Sakellaropoulos
authors.affiliation: Department of Pharmacology, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors.forename: Peristera-Ioanna
authors.initials: PI
authors.lastname: Petropoulou
authors.affiliation: Department of Pharmacology, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors.forename: Caterina
authors.initials: C
authors.lastname: Constantinou
authors.affiliation: INSERM UMR_S 1166-ICAN , Faculté de Médecine Pitié-Salpêtrière, 91 Bd de l'Hôpital, 75013 Paris, France.
authors.forename: Anatol
authors.initials: A
authors.lastname: Kontush
authors.affiliation: Department of Pharmacology, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors.forename: Kyriakos E
authors.initials: KE
authors.lastname: Kypreos
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000502:physiology*; D001057:Apolipoproteins E / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008055:Lipids; D008075:Lipoproteins, HDL; D002784:Cholesterol