title: Orally administered eicosapentaenoic acid induces rapid regression of atherosclerosis via modulating the phenotype of dendritic cells in LDL receptor-deficient mice.
abstract: OBJECTIVE
  Eicosapentaenoic acid (EPA) has been shown to have beneficial effects on cardiovascular diseases, although the precise mechanism is unknown. We investigated the effect of EPA on the regression of atherosclerosis.
  
  
  RESULTS
  LDL-receptor-deficient mice were fed a high-cholesterol diet for 8 weeks to build up aortic sinus atherosclerotic lesions and then were fed a normal diet with or without 5% EPA for 4 weeks. Atherosclerotic lesions were histologically assessed, and immunologic assays were performed. EPA treatment significantly regressed atherosclerosis (-22.7%, P<0.05) and decreased the content of macrophages, CD4(+) T cells, and dendritic cells (DCs) in atherosclerotic lesions, though only changing the chow never induced the regression. Flow cytometric analysis revealed that EPA increased immature DCs (CD11c(+) CD80(-) CD86(-)), increased the indoleamine 2,3-dioxygenase (IDO) in DCs, and decreased the number of CD4(+) T cells. In the presence of the IDO inhibitor, the beneficial effects of EPA on regression were inhibited, suggesting that the effect of EPA was mainly mediated through IDO.
  
  
  CONCLUSIONS
  In addition to lowering plasma cholesterol, EPA regressed atherosclerosis probably due to modulation of DC phenotype and reduction in T cell numbers. The present findings might partly explain the beneficial effects of EPA in clinics and support clinical evidence.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakajima
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kita
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takeda
authors.forename: Naoto
authors.initials: N
authors.lastname: Sasaki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kasahara
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shinohara
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Rikitake
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishida
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000284:Administration, Oral; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D003713:Dendritic Cells / Q000502:physiology*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000502:physiology; D008297:Male; D051379:Mice; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000172:deficiency*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D011973:Receptors, LDL; D015118:Eicosapentaenoic Acid