title: Effects of HMGB1 on ischemia-reperfusion injury in the rat heart.
abstract: BACKGROUND
  Coronary ischemia-reperfusion (I/R) injury causes cardiomyocyte necrosis in a multi-step process that includes an inflammatory reaction. A recent study has suggested that high-mobility group box 1 (HMGB1) is a late mediator of lethal sepsis and an early mediator of inflammation and necrosis following I/R injury. In the present study a neutralizing monoclonal antibody (mAb) for HMGB1 was used to clarify the role of HMGB1 in cardiac I/R injury.
  
  
  RESULTS
  Rats underwent 30 min of left coronary artery occlusion followed by 60 min reperfusion. An intravenous injection of anti-HMGB1 mAb or control IgG was administered just before reperfusion. The infarct size was enlarged in the anti-HMGB1 mAb group in comparison with the control group (p<0.05). The treatment of anti-HMGB1 mAb significantly increased the plasma troponin-T and norepinephrine (NE) content in the heart in comparison with the control (p<0.05). Moreover, the production of dihydroxyphenylglycol was reduced in the anti-HMGB1-treated group (p<0.05).
  
  
  CONCLUSIONS
  This study shows for the first time the effects of treatment with neutralizing anti-HMGB1 mAb on I/R injury in the rat heart. The findings support the novel view that I/R-induced HMGB1 may be an important factor in the modulation of interstitial NE.
authors.affiliation: Department of Cardiovascular Surgery, University of Okayama Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. gmd16008@cc-okayama-u.ac.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Oozawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Mori
authors.forename: Toru
authors.initials: T
authors.lastname: Kanke
authors.forename: Hideo
authors.initials: H
authors.lastname: Takahashi
authors.forename: Keyue
authors.initials: K
authors.lastname: Liu
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tomono
authors.forename: Masato
authors.initials: M
authors.lastname: Asanuma
authors.forename: Ikuko
authors.initials: I
authors.lastname: Miyazaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
authors.forename: Shunji
authors.initials: S
authors.lastname: Sano
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000276:immunology* / Q000378:metabolism*; D007074:Immunoglobulin G / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009205:Myocarditis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D024243:HMGB1 Protein; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D009638:Norepinephrine