title: Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice.
abstract: Naringin (NAR) from grapefruit has exhibited potential protective effects against atherosclerosis development. However, specific mechanisms responsible for such effects are poorly understood. Thus, we aimed to investigate the antiatherogenic effects of NAR in different mouse models of hypercholesterolemia and decipher its molecular targets in the aorta using transcriptomic approach. Two mouse models of hypercholesterolemia, wild-type mice fed a high-fat/high-cholesterol diet and apolipoprotein E-deficient mice fed a semisynthetic diet, were studied. Mice were fed a respective control diets supplemented or not for 18 weeks with 0.02% of NAR, that is, nutritional supplementation. NAR supplementation reduced plaque progression only in wild-type mice fed the high-fat/high-cholesterol diet (-41%). Consistent with this protective effect, NAR reduced plasma non-high-density lipoprotein cholesterol concentrations as well as biomarkers of endothelial dysfunction. Microarray studies performed on aortas demonstrated differentially expressed genes encoding proteins involved in cell adhesion, actin cytoskeleton organization and cell division. Thus, the changes in gene expression induced by NAR could suggest a limited atherosclerosis progression by preventing immune cell adhesion and infiltration in the intima of vascular wall, as well as smooth muscle cell proliferation. Furthermore, this hypothesis was strengthened by in vitro experiments, which showed the ability of naringenin to reduce monocyte adhesion to endothelial cells and smooth muscle cell proliferation. In conclusion, this study revealed the antiatherogenic effect of NAR supplemented at a nutritionally achievable dose, specifically toward diet-induced atherosclerosis, and depicted its multitarget mode of action at the vascular level.
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Chanet
authors.forename: Dragan
authors.initials: D
authors.lastname: Milenkovic
authors.forename: Christiane
authors.initials: C
authors.lastname: Deval
authors.forename: Mylène
authors.initials: M
authors.lastname: Potier
authors.forename: Joël
authors.initials: J
authors.lastname: Constans
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mazur
authors.forename: Catherine
authors.initials: C
authors.lastname: Bennetau-Pelissero
authors.forename: Christine
authors.initials: C
authors.lastname: Morand
authors.forename: Annie M
authors.initials: AM
authors.lastname: Bérard
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D032083:Citrus paradisi / Q000737:chemistry*; D004036:Diet, Atherogenic; D042783:Endothelial Cells / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism
chemical_list: D044950:Flavanones; C005274:naringin