title: Relationship between vascular reactivity and expression of HMGB1 in a rat model of septic aorta.
abstract: BACKGROUND
  High mobility group box 1 (HMGB1), a ubiquitous nuclear protein, induces several inflammatory diseases and functions as a fatal factor when released extracellularly. The effect of HMGB1 on vascular reactivity during sepsis remains to be clarified.
  
  
  METHODS
  A rat model of abdominal sepsis was produced by cecal ligation and puncture (CLP) under sevoflurane anesthesia (n = 28). Anti-HMGB1 antibody at a dose of 4 or 0.4 mg/kg, or normal saline was injected twice intravenously, i.e., immediately after the CLP surgery and 4 h thereafter. Rats in the sham group underwent laparotomy, and the cecum was manipulated but not ligated or punctured. The descending thoracic aorta was excised 12 h after the CLP surgery and cut into rings of approximately 3 mm in length. Changes in the expression of HMGB1 and vascular reactivity were examined in the rings shortly after harvest and 4 h thereafter.
  
  
  RESULTS
  HMGB1 was identified immunohistochemically and by Western blotting in the nuclei of vascular endothelial and smooth muscle cells in all groups shortly after excision of the aorta, but its expression was augmented only in the CLP groups 4 h thereafter. Degenerated smooth muscle cells were also observed after CLP. Anti-HMGB1 antibody dose-dependently inhibited the augmentation of HMGB1 expression and the morphological changes induced by CLP. The expression of HMGB1 partly correlated with suppression of vascular reactivity.
  
  
  CONCLUSIONS
  The present results strongly suggest that HMGB1 plays an important role in vascular malfunction from an early phase of sepsis.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Kanazawa Medical University, Daigaku 1-1, Uchinada, Ishikawa, 920-0293, Japan, rorry@kanazawa-med.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishiike
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hiramatsu
authors.forename: Miharu
authors.initials: M
authors.lastname: Shiraishi
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Ueda
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tsuchida
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000503:physiopathology* / Q000601:surgery; D002432:Cecum / Q000503:physiopathology / Q000601:surgery; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology* / Q000601:surgery; D024243:HMGB1 Protein / Q000096:biosynthesis* / Q000235:genetics; D008026:Ligation / Q000379:methods; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery
chemical_list: D024243:HMGB1 Protein; C104200:Hbp1 protein, rat