Effects of HMGB1 on ischemia-reperfusion injury in the rat heart.
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.
Oozawa
Susumu
S
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
Mori
Shuji
S
Kanke
Toru
T
Takahashi
Hideo
H
Liu
Keyue
K
Tomono
Yasuko
Y
Asanuma
Masato
M
Miyazaki
Ikuko
I
Nishibori
Masahiro
M
Sano
Shunji
S
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
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