title: Docosahexaenoic acid supplementation modifies fatty acid incorporation in tissues and prevents hypoxia induced-atherosclerosis progression in apolipoprotein-E deficient mice.
abstract: The n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), displays anti-inflammatory properties that may prevent atherosclerosis progression. Exposure of apolipoprotein-E deficient (ApoE(-/-)) mice to chronic intermittent hypoxia (CIH) accelerates atherosclerosis progression. Our aim was to assess DHA-supplementation influence on fatty acid incorporation in different tissues/organs and on atherosclerosis progression in ApoE(-/-) mice exposed to CIH. ApoE(-/-) mice were exposed to CIH or normoxia (N) and randomized to four groups (N control, CIH control, N+DHA, and CIH+DHA). DHA-supplementation enhanced DHA and reduced arachidonic acid (AA) contents in tissues/organs. CIH control mice exhibited increased atherosclerosis lesion sizes compared to N control mice. DHA prevented CIH induced atherosclerosis but did not improve atherosclerosis burden in N mice. Aortic matrix metalloproteinase-2 (MMP-2) expression was decreased in CIH+DHA mice (p=0.007). DHA-supplementation prevented CIH-induced atherosclerosis acceleration. This was associated with a decrease of AA incorporation and of aortic MMP-2 gene expression.
authors.affiliation: Université Grenoble Alpes, F-38041 Grenoble, France; INSERM U1042, HP2, F-38041 Grenoble, France; CHU, Hôpital A. Michalon, Département de Biochimie, Toxicologie et Pharmacologie, CS 10217, F-38043 Grenoble cedex 9, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Van Noolen
authors.affiliation: Department of Medicine, Karolinska Institutet, 17176 Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Bäck
authors.affiliation: Université Grenoble Alpes, F-38041 Grenoble, France; INSERM U1042, HP2, F-38041 Grenoble, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Arnaud
authors.affiliation: CHU, Hôpital A. Michalon, Département de Biochimie, Toxicologie et Pharmacologie, CS 10217, F-38043 Grenoble cedex 9, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Rey
authors.affiliation: Department of Medicine, Karolinska Institutet, 17176 Stockholm, Sweden.
authors.forename: Marcelo H
authors.initials: MH
authors.lastname: Petri
authors.affiliation: Université Grenoble Alpes, F-38041 Grenoble, France; INSERM U1042, HP2, F-38041 Grenoble, France; CHU, Hôpital A. Michalon, Département de Biochimie, Toxicologie et Pharmacologie, CS 10217, F-38043 Grenoble cedex 9, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Levy
authors.affiliation: Université Grenoble Alpes, F-38041 Grenoble, France; INSERM U1042, HP2, F-38041 Grenoble, France; CHU, Hôpital A. Michalon, Département de Biochimie, Toxicologie et Pharmacologie, CS 10217, F-38043 Grenoble cedex 9, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Faure
authors.affiliation: Université Grenoble Alpes, F-38041 Grenoble, France; INSERM U1042, HP2, F-38041 Grenoble, France; CHU, Hôpital A. Michalon, Département de Biochimie, Toxicologie et Pharmacologie, CS 10217, F-38043 Grenoble cedex 9, France. Electronic address: FStanke@chu-grenoble.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Stanke-Labesque
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D005227:Fatty Acids / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: D001057:Apolipoproteins E; D005227:Fatty Acids; D004281:Docosahexaenoic Acids
keywords: Atherosclerosis; Docosahexaenoic acid; Eicosapentaenoic acid; Inflammation; Intermittent hypoxia; Omega 3 polyunsaturated fatty acid