title: Contrasting effects of arachidonic acid and docosahexaenoic acid membrane incorporation into cardiomyocytes on free cholesterol turnover.
abstract: The preservation of a constant pool of free cholesterol (FC) is critical to ensure several functions of cardiomyocytes. We investigated the impact of the membrane incorporation of arachidonic acid (C20:4 ω6, AA) or docosahexaenoic acid (C22:6 ω3, DHA) as ω6 or ω3 polyunsaturated fatty acids (PUFAs) on cholesterol homeostasis in primary cultures of neonatal rat cardiac myocytes. We measured significant alterations to the phospholipid FA profiles, which had markedly different ω6/ω3 ratios between the AA and DHA cells (13 vs. 1). The AA cells showed a 2.7-fold lower cholesterol biosynthesis than the DHA cells. Overall, the AA cells showed 2-fold lower FC masses and 2-fold higher cholesteryl ester masses than the DHA cells. The AA cells had a lower FC to phospholipid ratio and higher triglyceride levels than the DHA cells. Moreover, the AA cells showed a 40% decrease in ATP binding cassette transporter A1 (ABCA1)-mediated and a 19% decrease in ABCG1-mediated cholesterol efflux than the DHA cells. The differences in cholesterol efflux pathways induced by AA or DHA incorporation were not caused by variations in ABCs transporter expression and were reduced when ABC transporters were overexpressed by exposure to LXR/RXR agonists. These results show that AA incorporation into cardiomyocyte membranes decreased the FC turnover by markedly decreasing the endogenous cholesterol synthesis and by decreasing the ABCA1- and ABCG1-cholesterol efflux pathways, whereas DHA had the opposite effects. We propose that these observations may partially contribute to the beneficial effects on the heart of a diet containing a high ω3/ω6 PUFA ratio.
authors.affiliation: Univ Paris-Sud, EA 4529, UFR de Pharmacie, 92296 Châtenay-Malabry, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Doublet
authors.affiliation: INRA, UMR 1319 MICALIS, Commensal and Probiotics-Host Interactions Laboratory, 78350 Jouy-en-Josas, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Robert
authors.affiliation: AP-HP (Assistance Publique-Hôpitaux de Paris), Hôpital européen Georges Pompidou, Service de Biochimie, 75015 Paris, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Vedie
authors.affiliation: INRA, UMR 1198 Biologie du Développement et Reproduction, 78352 Jouy-en-Josas, France; ENVA, 94700 Maisons Alfort, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Rousseau-Ralliard
authors.affiliation: Univ Paris-Sud, EA 4529, UFR de Pharmacie, 92296 Châtenay-Malabry, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Reboulleau
authors.affiliation: CRNH-IdF, SMBH Université Paris 13, 93000 Bobigny, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Grynberg
authors.affiliation: Univ Paris-Sud, EA 4529, UFR de Pharmacie, 92296 Châtenay-Malabry, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Hôpital européen Georges Pompidou, Service de Biochimie, 75015 Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Paul
authors.affiliation: Univ Paris-Sud, EA 4529, UFR de Pharmacie, 92296 Châtenay-Malabry, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Hôpital européen Georges Pompidou, Service de Biochimie, 75015 Paris, France. Electronic address: natalie_fournier@yahoo.fr.
authors.forename: Natalie
authors.initials: N
authors.lastname: Fournier
keywords: ATP binding cassette transporter A1; Arachidonic ω6 polyunsaturated fatty acid; Cardiomyocytes; Cholesterol efflux; Cholesterol homeostasis; Docosahexaenoic ω3 polyunsaturated fatty acid