title: The phenotype of infiltrating macrophages influences arteriosclerotic plaque vulnerability in the carotid artery.
abstract: BACKGROUND
  Proinflammatory (M1) macrophages and anti-inflammatory (M2) macrophages have been identified in atherosclerotic plaques. While these macrophages have been speculated to be related to plaque vulnerability, there are limited studies investigating this relationship. Therefore, we examined the association between macrophage phenotype (M1 versus M2) and plaque vulnerability and clinical events.
  
  
  METHODS
  Patients undergoing carotid endarterectomy received an ultrasound of the carotid artery before surgery. Plaques were processed for analysis by immunohistochemistry, Western blotting, and real-time polymerase chain reaction studies. Medical history and clinical data were obtained from medical records.
  
  
  RESULTS
  Patients were divided into 2 groups: those suffering from acute ischemic attack (symptomatic, n = 31) and those that did not present with symptoms (asymptomatic, n = 34). Ultrasound analysis revealed that plaque vulnerability was greater in the symptomatic group (P= .033; Chi-square test). Immunohistochemistry revealed that plaques from the symptomatic group had a greater concentration of M1 macrophages (CD68-, CD11c-positive) while plaques from the asymptomatic group had more M2 macrophages (CD163-positive). This observation was confirmed by Western blotting. Characterization by real-time polymerase chain reaction studies revealed that plaques from the symptomatic group had increased expression of the M1 markers CD68 and CD11c, as well as monocyte chemoattractive protein-1, interleukin-6, and matrix metalloproteinase-9. In addition, more M1 macrophages expressed in unstable plaques were defined by ultrasound analysis, while more M2 macrophages were expressed in stable plaques.
  
  
  CONCLUSIONS
  Our data show that M1 macrophage content of atherosclerotic plaques is associated with clinical incidence of ischemic stroke and increased inflammation or fibrinolysis. We also show the benefits of using ultrasound to evaluate vulnerability in the plaques.
authors.affiliation: Department of Internal Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Kyu Yong
authors.initials: KY
authors.lastname: Cho
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuroda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yasuda
authors.forename: Kenji
authors.initials: K
authors.lastname: Kamiyama
authors.forename: Joji
authors.initials: J
authors.lastname: Nakagawara
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takigami
authors.forename: Takuma
authors.initials: T
authors.lastname: Kondo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D014463:Ultrasonography; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039521:CD11c Antigen; D015850:Interleukin-6; D020780:Matrix Metalloproteinase 9; C067980:CD68 antigen, human; D000097382:CD68 Molecule