Key result
Treatment with neutralizing anti-HMGB1 monoclonal antibody significantly increased infarct size by 31% compared to control IgG in a rat model of myocardial ischemia-reperfusion injury.
Why the study?
Does neutralizing anti-HMGB1 mAb reduce infarct size in a rat model of myocardial ischemia-reperfusion injury?
Does neutralizing anti-HMGB1 mAb reduce infarct size in a rat model of myocardial ischemia-reperfusion injury?
Effect estimate: 31% greater relative infarct size
Absolute Event Rate: 53.7% vs 40.9%
p-value: p=<0.05
Treatment with neutralizing anti-HMGB1 mAb unexpectedly exacerbated ischemia-reperfusion injury and increased infarct size in rat hearts, likely by modulating interstitial norepinephrine dynamics.
May worsen ischemia-reperfusion injury; hypothesis-generating for HMGB1's protective role before clinical translation.
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. METHODS AND 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). CONCLUSION: 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.
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Oozawa et al. (2008) studied Myocardial ischemia-reperfusion injury (n=39). Anti-HMGB1 monoclonal antibody vs. Control IgG (class-matched mAb against keyhole limpet hemocyanin) was evaluated on Infarct size as a percentage of the at-risk area (31% greater relative infarct size, p=<0.05). Treatment with neutralizing anti-HMGB1 monoclonal antibody significantly increased infarct size by 31% compared to control IgG in a rat model of myocardial ischemia-reperfusion injury.
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