title: Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability.
abstract: OBJECTIVE
  To examine n-3 polyunsaturated fatty acid (PUFA) incorporation into atherosclerotic plaques and the association with plaque inflammation and stability.
  
  
  RESULTS
  Patients awaiting carotid endarterectomy (n=121) were randomised to consume control capsules or n-3 PUFA ethyl ester capsules until surgery (median 21 days). The fatty acid compositions of plasma and carotid plaque phospholipids, plaque features, and expression of inflammatory genes were determined. The proportion of eicosapentaenoic acid (EPA) was higher (P<0.0001) in carotid plaque phospholipids in patients in the n-3 PUFA group. Plaques from patients in the n-3 PUFA group had fewer foam cells (P=0.0390). There were no other differences between plaques in the two groups with regard to histological characteristics or morphology. Plaque stability was not different between the two groups. However, the EPA content of plaque phospholipids was inversely associated with plaque instability (P=0.0209), plaque inflammation (P=0.0108), the number of T cells in the plaque (P=0.0097) and a summary score considering a range of plaque features (P=0.0425). Plaques from patients who received n-3 PUFAs had significantly lower levels of mRNA for matrix metalloproteinases (MMP)-7 (P=0.0055), -9 (P=0.0048) and -12 (P=0.0044) and for interleukin-6 (P=0.0395) and intercellular adhesion molecule 1 (P=0.0142).
  
  
  CONCLUSIONS
  Atherosclerotic plaques readily incorporate EPA. A higher plaque EPA content is associated with a reduced number of foam cells and T cells, less inflammation and increased stability.
authors.affiliation: School of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Abbie L
authors.initials: AL
authors.lastname: Cawood
authors.forename: Ren
authors.initials: R
authors.lastname: Ding
authors.forename: Frances L
authors.initials: FL
authors.lastname: Napper
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Young
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Williams
authors.forename: Matthew J A
authors.initials: MJ
authors.lastname: Ward
authors.forename: Ola
authors.initials: O
authors.lastname: Gudmundsen
authors.forename: Runar
authors.initials: R
authors.lastname: Vige
authors.forename: Simon P K
authors.initials: SP
authors.lastname: Payne
authors.forename: Shu
authors.initials: S
authors.lastname: Ye
authors.forename: Ciff P
authors.initials: CP
authors.lastname: Shearman
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Gallagher
authors.forename: Robert F
authors.initials: RF
authors.lastname: Grimble
authors.forename: Philip C
authors.initials: PC
authors.lastname: Calder
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002214:Capsules; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016009:Chi-Square Distribution; D016207:Cytokines / Q000235:genetics; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000097:blood; D004311:Double-Blind Method; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D016894:Endarterectomy, Carotid; D004739:England; D005260:Female; D005487:Foam Cells / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism; D011300:Preoperative Care; D012333:RNA, Messenger / Q000032:analysis; D012422:Rupture, Spontaneous; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D002214:Capsules; D016207:Cytokines; D004338:Drug Combinations; D018836:Inflammation Mediators; D010743:Phospholipids; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid; C405603:Omacor; D020782:Matrix Metalloproteinases