title: Deleterious impact of elaidic fatty acid on ABCA1-mediated cholesterol efflux from mouse and human macrophages.
abstract: Consumption of trans fatty acids (TFA) increase cardiovascular risk more than do saturated FA, but the mechanisms explaining their atherogenicity are still unclear. We investigated the impact of membrane incorporation of TFA on cholesterol efflux by exposing J774 mouse macrophages or human monocyte-derived macrophages (HMDM) to media enriched or not (standard medium) with industrially produced elaidic (trans-9 18:1) acid, naturally produced vaccenic (trans-11 18:1) acid (34 h, 70 μM) or palmitic acid. In J774 macrophages, elaidic and palmitic acid, but not vaccenic acid, reduced ABCA1-mediated efflux by ~23% without affecting aqueous diffusion, SR-BI or ABCG1-mediated pathways, and this effect was maintained in cholesterol-loaded cells. The impact of elaidic acid on the ABCA1 pathway was weaker in cholesterol-normal HMDM, but elaidic acid induced a strong reduction of ABCA1-mediated efflux in cholesterol-loaded cells (-36%). In J774 cells, the FA supplies had no impact on cellular free cholesterol or cholesteryl ester masses, the abundance of ABCA1 mRNA or the total and plasma membrane ABCA1 protein content. Conversely, TFA or palmitic acid incorporation induced strong modifications of the membrane FA composition with a decrease in the ratio of (cis-monounsaturated FA+polyunsaturated FA):(saturated FA+TFA), with elaidic and vaccenic acids representing each 20% and 13% of the total FA composition, respectively. Moreover, we demonstrated that cellular ATP was required for the effect of elaidic acid, suggesting that it contributes to atherogenesis by impairing ABCA1-mediated cholesterol efflux in macrophages, likely by decreasing the membrane fluidity, which could thereby reduce ATPase activity and the function of the transporter.
authors.affiliation: Univ Paris-Sud, EA 4529, UFR de Pharmacie, 92296 Châtenay-Malabry, France. natalie_fournier@yahoo.fr
authors.forename: Natalie
authors.initials: N
authors.lastname: Fournier
authors.forename: Nesrine
authors.initials: N
authors.lastname: Attia
authors.forename: Delphine
authors.initials: D
authors.lastname: Rousseau-Ralliard
authors.forename: Benoît
authors.initials: B
authors.lastname: Vedie
authors.forename: Frédéric
authors.initials: F
authors.lastname: Destaillats
authors.forename: Alain
authors.initials: A
authors.lastname: Grynberg
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Paul
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D018955:CD36 Antigens / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D004058:Diffusion / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology; D019301:Oleic Acid / Q000494:pharmacology*; D009829:Oleic Acids / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D018955:CD36 Antigens; D009829:Oleic Acids; D010743:Phospholipids; D012333:RNA, Messenger; D019301:Oleic Acid; C011459:elaidic acid; D000255:Adenosine Triphosphate; D002784:Cholesterol; C050413:11-octadecenoic acid