title: Administration of high dose eicosapentaenoic acid enhances anti-inflammatory properties of high-density lipoprotein in Japanese patients with dyslipidemia.
abstract: OBJECTIVE
  It has been reported that high-density lipoprotein (HDL) loses anti-inflammatory function and promotes atherosclerosis under pathological conditions. However, no pharmacological therapy to improve HDL function is currently available. We aimed to evaluate the effect of oral administration of eicosapentaenoic acid (EPA) on HDL function.
  
  
  METHODS
  Japanese patients with dyslipidemia were treated with EPA (1800 mg/day, 4 weeks), and anti-inflammatory functions of HDL were assessed utilizing in vitro cell-based assays.
  
  
  RESULTS
  The EPA treatment did not change serum cholesterol and triglyceride levels, but it significantly increased EPA concentrations in the serum and HDL fraction. The EPA/arachidonic acid ratio in the HDL was in proportion to that in the serum, suggesting that the orally administered EPA was efficiently incorporated into the HDL particles. The HDL after EPA treatment showed significantly increased activity of anti-oxidative enzyme, paraoxonase-1. In addition, the EPA-rich HDL significantly improved endothelial cell migration, and markedly inhibited cytokine-induced expression of vascular cell adhesion molecule-1, in human umbilical vein endothelial cells, compared to HDL before the EPA treatment. Moreover, the EPA-rich HDL augmented cholesterol efflux capacity from macrophages.
  
  
  CONCLUSIONS
  Oral administration of EPA regenerated anti-oxidative and anti-inflammatory functions of HDL, and promoted cholesterol efflux from macrophages. Therefore, EPA may transform "dysfunctional HDL" to "functional", in patients with coronary risk factors.
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: ishida@med.kobe-u.ac.jp.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Nagao
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Takeshige
authors.initials: T
authors.lastname: Mori
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Monguchi
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Mori
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Honjo
authors.affiliation: Division of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Irino
authors.affiliation: Division of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Toh
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000097:blood*; D000975:Antioxidants / Q000737:chemistry; D043303:Aryldialkylphosphatase / Q000378:metabolism; D050197:Atherosclerosis / Q000503:physiopathology; D002465:Cell Movement; D002784:Cholesterol / Q000378:metabolism; D050171:Dyslipidemias / Q000097:blood*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D007564:Japan; D008075:Lipoproteins, HDL / Q000097:blood*; D008264:Macrophages / Q000166:cytology; D008297:Male; D008875:Middle Aged; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008075:Lipoproteins, HDL; D019010:Vascular Cell Adhesion Molecule-1; D002784:Cholesterol; D015118:Eicosapentaenoic Acid; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Adhesion molecule; Cholesterol efflux; Dysfunctional HDL; Eicosapentaenoic acid; High-density lipoprotein; Paraoxonase; n-3 fatty acid