title: The "atheroprotective" mediators apolipoprotein A-I and Foxp3 are over-abundant in unstable carotid plaques.
abstract: OBJECTIVE
  Inflammation is important in plaque vulnerability but the role of atheroprotective mediators in unstable plaques is not defined. The apolipoproteinA-I (apoA-I) component of HDL, and CD4+/CD25+ regulatory T cells (with their major transcription factor, Foxp3), have been implicated in the suppression of vascular inflammation. Our aim was to characterise the presence of these novel "protective" markers (apoA-I and Foxp3) in carotid plaques from symptomatic and asymptomatic subjects.
  
  
  RESULTS
  Plaques from 57 patients (25 symptomatic, 32 asymptomatic) were stained immunohistochemically for macrophages (CD68), T cells (CD3), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), myeloperoxidase (MPO), apoA-I and Foxp3. Twelve randomly selected plaques (6 asymptomatic, 6 symptomatic) were immunostained for interleukin-10 (IL-10) and interleukin-17 (IL-17). Staining was quantified using Image-Pro Plus software. Significantly greater areas of positive immunostaining for CD68, CD3, MCP-1, MMP-2, IL-17 and MPO were found in plaques from symptomatic patients compared with asymptomatic patients (p<0.05 for all). Furthermore, significantly greater areas of positive immunostaining for apoA-I, Foxp3 and IL-10 were found in symptomatic versus asymptomatic plaques (p<0.05 for all). The presence of apoA-I was correlated significantly and co-localised with CD3, CD68, MCP-1, MMP-2 and MPO immunostaining (R=0.70, 0.63, 0.52, 0.55 and 0.79, respectively; p<0.01 for all). Foxp3 immunostaining also correlated significantly with CD3 (R=0.42), CD68 (R=0.47), MCP-1 (R=0.55) and MMP-2 (R=0.44) immunostaining (p<0.05 for all).
  
  
  CONCLUSIONS
  ApoA-I and Foxp3 are over-abundant in plaques from symptomatic subjects and co-localise with key inflammatory mediators. These data suggest ineffective/insufficient protection against atherosclerosis-mediated inflammation by these "atheroprotective" moieties.
authors.affiliation: Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia; Discipline of Medicine, University of Sydney, Sydney, Australia; Discipline of Pathology, Bosch Institute, University of Sydney, Sydney, Australia. Electronic address: sanjay.patel@bigpond.com.
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.affiliation: Discipline of Pathology, Bosch Institute, University of Sydney, Sydney, Australia.
authors.forename: S H
authors.initials: SH
authors.lastname: Chung
authors.affiliation: Department of Vascular Surgery, Royal Prince Alfred Hospital, Sydney, Australia; Discipline of Surgery, University of Sydney, Sydney, Australia.
authors.forename: G
authors.initials: G
authors.lastname: White
authors.affiliation: Discipline of Pathology, Bosch Institute, University of Sydney, Sydney, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Bao
authors.affiliation: Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia; Discipline of Medicine, University of Sydney, Sydney, Australia.
authors.forename: D S
authors.initials: DS
authors.lastname: Celermajer
mesh_terms: D000368:Aged; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000502:physiology*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D016893:Carotid Stenosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D008297:Male
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors