title: Coexistence of foam cells and hypocholesterolemia in mice lacking the ABC transporters A1 and G1.
abstract: The concept that macrophages can become foam cells as a result of a disturbed balance between the uptake of cholesterol from lipoproteins and cholesterol efflux is generally accepted. ABCA1 and ABCG1 are two cholesterol transporters that may act sequentially to remove cellular cholesterol, but currently their combined role in vivo is unknown. We report here that targeted disruption of both ABCA1 and ABCG1 in mice, despite severe plasma hypocholesterolemia, leads to massive lipid accumulation and foam cell formation of tissue macrophages. A complete ablation of cellular cholesterol efflux in vitro is observed, whereas in vivo macrophage-specific reverse cholesterol transport to the feces is markedly decreased. Despite the massive foam cell formation of tissue macrophages, no lipid accumulation was observed in the vascular wall, even in mice of 1 year old, indicating that the double knockout mice, possibly because of their hypocholesterolemia, lack the trigger to attract macrophages to the vessel wall. In conclusion, even under hypocholesterolemic conditions macrophages can be converted into foam cells, and ABCA1 and ABCG1 play an essential role in the prevention of foam cell formation.
authors.affiliation: Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands. r.out@lacdr.leidenuniv.nl
authors.forename: Ruud
authors.initials: R
authors.lastname: Out
authors.forename: Wendy
authors.initials: W
authors.lastname: Jessup
authors.forename: Wilfried
authors.initials: W
authors.lastname: Le Goff
authors.forename: Menno
authors.initials: M
authors.lastname: Hoekstra
authors.forename: Ingrid C
authors.initials: IC
authors.lastname: Gelissen
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Leonard
authors.initials: L
authors.lastname: Kritharides
authors.forename: Giovanna
authors.initials: G
authors.lastname: Chimini
authors.forename: Johan
authors.initials: J
authors.lastname: Kuiper
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Thierry
authors.initials: T
authors.lastname: Huby
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: Van Berkel
authors.forename: Miranda
authors.initials: M
authors.lastname: Van Eck
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D050171:Dyslipidemias / Q000209:etiology*; D005487:Foam Cells / Q000166:cytology*; D008055:Lipids / Q000032:analysis; D008074:Lipoproteins / Q000172:deficiency; D008264:Macrophages; D051379:Mice; D018345:Mice, Knockout
chemical_list: C487540:ABCG1 protein, mouse; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D008055:Lipids; D008074:Lipoproteins; D002784:Cholesterol