title: Reduced effect on apoptosis of 4-hydroxyhexenal and oxidized LDL enriched with n-3 fatty acids from postmenopausal women.
abstract: BACKGROUND
  Oxidized low-density lipoprotein (oxLDL) promotes apoptosis in atherosclerotic plaques in the vascular wall, a process mediated through its oxidized lipids. 4-Hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE), derived from oxidation of n-6 and n-3 fatty acids, respectively, are among the major oxidized products in oxLDL.
  
  
  OBJECTIVE
  This study hypothesized that eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA)-rich versus linoleic acid-rich oxLDL obtained from postmenopausal women and HNE versus HHE differentially influence apoptosis in U937 cells.
  
  
  METHODS
  Thirty healthy postmenopausal women were supplemented with 14 g/day safflower oil (SO), 7 g/day of both fish oil and SO (low dose LFO) or 14 g/day fish oil (high dose HFO) for 5 weeks. Low-density lipoprotein, obtained after supplementation, was oxidized with 5 microM CuSO(4) at 37 degrees C for 6 h. The concentration of cholesteryl ester hydroperoxides (CEOOH) and conjugated dienes was measured in the oxidized LDL (oxLDL). U937 cells were incubated with the oxLDL, 10 microM of HHE, 7 muM of HHE plus 3 microM of HNE, 5 microM of both HHE and HNE or 10 microM of HNE and the extent of apoptosis measured three ways.
  
  
  RESULTS
  The concentration of CEOOH and conjugated dienes in oxLDL did not differ among the three treatment groups. The percent of apoptotic cells was approximately 40% lower when incubated with oxLDL obtained from the HFO-supplemented group than the SO-supplemented group measured by both the Annexin V and the DNA fragmentation assays (P = .04 and .004, respectively). Apoptosis of U937 cells was significantly lower in cells incubated with 10 microM of HHE, and mixtures of HHE and HNE than the 10 microM HNE when measured by the Annexin V, DNA fragmentation and 4,6-diamidino-2-phenylindole (DAPI) staining.
  
  
  CONCLUSIONS
  These data suggest that the cardioprotective properties of n-3 fatty acids may derive in part from their less reactive oxidized lipid metabolites.
authors.affiliation: Department of Nutrition, The University of North Carolina at Greensboro, P.O. Box 26170, Greensboro, NC 27402-6170, USA.
authors.forename: Ye-Sun
authors.initials: YS
authors.lastname: Lee
authors.forename: Rosemary C
authors.initials: RC
authors.lastname: Wander
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D019587:Dietary Supplements; D005227:Fatty Acids / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause; D012450:Safflower Oil / Q000008:administration & dosage / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D012450:Safflower Oil