title: Dietary flaxseed inhibits atherosclerosis in the LDL receptor-deficient mouse in part through antiproliferative and anti-inflammatory actions.
abstract: Dietary flaxseed has been shown to have potent antiatherogenic effects in rabbits. The purpose of the present study was to investigate the antiatherogenic capacity of flaxseed in an animal model that more closely represents the human atherosclerotic condition, the LDL receptor-deficient mouse (LDLrKO), and to identify the cellular mechanisms for these effects. LDLrKO mice were administered a regular diet (RG), a 10% flaxseed-supplemented diet (FX), or an atherogenic diet containing 2% cholesterol alone (CH) or supplemented with 10% flaxseed (CF), 5% flaxseed (CF5), 1% flaxseed (CF1), or 5% coconut oil (CS) for 24 wk. LDLrKO mice fed a cholesterol-supplemented diet exhibited a rise in plasma cholesterol without a change in triglycerides and an increase in atherosclerotic plaque formation. The CS mice exhibited elevated levels of plasma cholesterol, triglycerides, and saturated fatty acids and an increase in plaque development. Supplementation of the cholesterol-enriched diet with 10% (wt/wt) ground flaxseed lowered plasma cholesterol and saturated fatty acids, increased plasma ALA, and inhibited plaque formation in the aorta and aortic sinus compared with mice fed a diet supplemented with only dietary cholesterol. The expression of proliferating cell nuclear antigen (PCNA) and the inflammatory markers IL-6, mac-3, and VCAM-1 was increased in aortic tissue from CH and CS mice. This expression was significantly reduced or normalized when flaxseed was included in the diet. Our results demonstrate that dietary flaxseed can inhibit atherosclerosis in the LDLrKO mouse through a reduction of circulating cholesterol levels and, at a cellular level, via antiproliferative and anti-inflammatory actions.
authors.affiliation: Canadian Center for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Center, Winnipeg, Canada.
authors.forename: Chantal M C
authors.initials: CM
authors.lastname: Dupasquier
authors.forename: Elena
authors.initials: E
authors.lastname: Dibrov
authors.forename: Annette L
authors.initials: AL
authors.lastname: Kneesh
authors.forename: Paul K M
authors.initials: PK
authors.lastname: Cheung
authors.forename: Kaitlin G Y
authors.initials: KG
authors.lastname: Lee
authors.forename: Helen K
authors.initials: HK
authors.lastname: Alexander
authors.forename: Behzad K
authors.initials: BK
authors.lastname: Yeganeh
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Moghadasian
authors.forename: Grant N
authors.initials: GN
authors.lastname: Pierce
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000943:Antigens, Differentiation / Q000378:metabolism; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects*; D004032:Diet; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D019597:Flax; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000378:metabolism; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008517:Phytotherapy; D028321:Plant Preparations / Q000494:pharmacology; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012639:Seeds; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000943:Antigens, Differentiation; D000960:Hypolipidemic Agents; D015850:Interleukin-6; D008055:Lipids; D028321:Plant Preparations; D011973:Receptors, LDL; D019010:Vascular Cell Adhesion Molecule-1; C036763:monocyte-macrophage differentiation antigen