title: Overexpression of eotaxin and the CCR3 receptor in human atherosclerosis: using genomic technology to identify a potential novel pathway of vascular inflammation.
abstract: BACKGROUND
  Unstable atherosclerotic lesions typically have an abundant inflammatory cell infiltrate, including activated T cells, macrophages, and mast cells, which may decrease plaque stability. The pathophysiology of inflammatory cell recruitment and activation in the human atheroma is incompletely described.
  
  
  RESULTS
  We hypothesized that differential gene expression with DNA microarray technology would identify new genes that may participate in vascular inflammation. RNA isolated from cultured human aortic smooth muscle cells treated with tumor necrosis factor-alpha (TNF-alpha) was examined with a DNA microarray with 8600 genes. This experiment and subsequent Northern analyses demonstrated marked increases in steady-state eotaxin mRNA (>20 fold), a chemokine initially described as a chemotactic factor for eosinophils. Because eosinophils are rarely present in human atherosclerosis, we then studied tissue samples from 7 normal and 14 atherosclerotic arteries. Immunohistochemical analysis demonstrated overexpression of eotaxin protein and its receptor, CCR3, in the human atheroma, with negligible expression in normal vessels. Eotaxin was predominantly located in smooth muscle cells. The CCR3 receptor was localized primarily to macrophage-rich regions as defined by immunopositivity for CD 68; a minority of mast cells also demonstrated immunopositivity for the CCR3 receptor.
  
  
  CONCLUSIONS
  Eotaxin and its receptor, CCR3, are overexpressed in human atherosclerosis, suggesting that eotaxin participates in vascular inflammation. These data demonstrate how genomic differential expression technology can identify novel genes that may participate in the stability of atherosclerotic lesions.
authors.affiliation: Respiratory Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Haley
authors.forename: C M
authors.initials: CM
authors.lastname: Lilly
authors.forename: J H
authors.initials: JH
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: S P
authors.initials: SP
authors.lastname: Kennedy
authors.forename: T G
authors.initials: TG
authors.lastname: Turi
authors.forename: J F
authors.initials: JF
authors.lastname: Thompson
authors.forename: G H
authors.initials: GH
authors.lastname: Sukhova
authors.forename: P
authors.initials: P
authors.lastname: Libby
authors.forename: R T
authors.initials: RT
authors.lastname: Lee
mesh_terms: D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015152:Blotting, Northern; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014657:Vasculitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; C515456:CCL11 protein, human; C515350:CCR3 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule