title: Possible involvement of Notch signaling in the pathogenesis of Buerger's disease.
abstract: OBJECTIVE
  Under pathological conditions, the Notch signal pathway is involved in the inflammatory process in arteriosclerosis, atherosclerosis and angiogenesis under ischemic conditions. The purpose of this study was to observe whether or not Buerger's disease is associated with Notch signal activation.
  
  
  METHODS
  All the patients were diagnosed between 1980 and 2009 at Nagoya University Hospital. Twenty-two specimens from 12 patients with Buerger's disease (TAO) and 13 specimens from nine patients with arteriosclerosis obliterans (ASO) were analyzed by immunohistochemistry for Notch1, Jagged-1 (a Notch ligand) and Hes-1 (a Notch 1 target transcription factor).
  
  
  RESULTS
  Notch1 and Jagged-1 were highly expressed in the endothelium in the new vasa vasorum and in the smooth muscle cells in the media of specimens from both groups. These Notch-related proteins were also remarkably expressed in inflammatory cells in the intima of specimens from TAO patients. Fewer inflammatory cells expressed Notch-related proteins in atheromatous plaques (Notch1 (%): 8.4 ± 0.76 versus 1.3 ± 0.43, P < 0.001; Jagged-1(%): 9.3 ± 1.1 versus 5.2 ± 1.1, P = 0.03). Indeed, Hes-1, which is a transcription factor downstream of Notch1, was remarkably expressed in the endothelium of new capillary vessels and inflammatory cells in TAO patients. Notch1-positive mononuclear cells were also seen in the thrombus in samples from the TAO group.
  
  
  CONCLUSIONS
  Our findings are the first demonstration that Notch signal activation in inflammatory cells may be involved in the pathophysiological mechanism underlying Buerger's disease.
authors.affiliation: Division of Vascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tamai
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kyousuke
authors.initials: K
authors.lastname: Takeshita
authors.forename: Akio
authors.initials: A
authors.lastname: Kodama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Banno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Narita
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Komori
mesh_terms: D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D013919:Thromboangiitis Obliterans / Q000235:genetics* / Q000378:metabolism; D000072056:Transcription Factor HES-1; D017539:Tunica Intima / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; C000606273:JAG1 protein, human; C497761:NOTCH1 protein, human; C078493:HES1 protein, human