title: Role of high-mobility group box 1 protein in post-infarction healing process and left ventricular remodelling.
abstract: OBJECTIVE
  High-mobility group box 1 protein (HMGB1) is one of the recently defined damage-associated molecular pattern molecules derived from necrotic cells and activated macrophages. We investigated clinical implications of serum HMGB1 elevation in patients with acute myocardial infarction (MI). Then, we evaluated the effect of HMGB1 blockade on post-MI left ventricular (LV) remodelling in a rat MI model.
  
  
  RESULTS
  Serum HMGB1 levels were examined in patients with ST-elevation MI (n = 35). A higher peak serum HMGB1 level was associated with pump failure, cardiac rupture, and in-hospital cardiac death. Then, an experimental MI model was induced in male Wistar rats. The mRNA and protein expression of HMGB1 were increased in the infarcted area compared with those values observed in sham-operated rats. We administered neutralizing anti-HMGB1 antibody (MI/anti-H) or control antibody (MI/C) to MI rats subcutaneously for 7 days. The mRNA levels of tumour necrosis factor-alpha and interleukin-1beta and the number of macrophages in the infarcted area were reduced on day 3 in MI/anti-H rats compared with MI/C rats. Interestingly, HMGB1 blockade resulted in thinning and expansion of the infarct scar and marked hypertrophy of the non-infarcted area on day 14.
  
  
  CONCLUSIONS
  Elevated serum HMGB1 levels were associated with adverse clinical outcomes in patients with MI. However, HMGB1 blockade in a rat MI model aggravated LV remodelling, possibly through impairment of the infarct-healing process. HMGB1, a novel predictor of adverse clinical outcomes after MI, may have an essential role in the appropriate healing process after MI.
authors.affiliation: Cardiopulmonary Division, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Anzai
authors.forename: Kotaro
authors.initials: K
authors.lastname: Naito
authors.forename: Taku
authors.initials: T
authors.lastname: Miyasho
authors.forename: Minoru
authors.initials: M
authors.lastname: Okamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokota
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamada
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000906:Antibodies; D002097:C-Reactive Protein / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D024243:HMGB1 Protein / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D020257:Ventricular Remodeling; D014945:Wound Healing
chemical_list: D000906:Antibodies; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D003402:Creatine Kinase