Background: High-mobility group box (HMGB) family is related to inflammatory diseases. We investigated whether serum HMGB2 levels are related to myocardial infarction (MI) severity and major adverse cardiac events (MACE) during MI. Methods and Results: We included 432 consecutive patients with ST-segment elevation myocardial infarction and 312 controls. Serum HMGB2 levels were significantly higher in MI patients than in controls. Increased HMGB2 levels were associated with MACE and negatively with ejection fraction in MI patients. HMGB2 was an independent determinant of MACE in logistic regression analysis. HMGB2 protein (10 μg) or saline was injected intramyocardially in MI rats, with or without co-administration of NADPH oxidase inhibitor apocynin. After 72 hours, pathologic, echocardiographic and hemodynamic examinations showed that HMGB2 increased infarct size and worsened cardiac function in MI rats. Moreover, HMGB2 administration enhanced reactive oxygen species (ROS) production, cell apoptosis, inflammation, and autophagosome clearance impairment, which were attenuated by co-administration of apocynin or knockdown of Receptor for Advanced Glycation End-products (RAGE). Conclusion: Increased serum HMGB2 levels are associated with MI severity and MACE at 1 month. HMGB2 promotes myocardial ischemic injury in rats and hypoxic H9C2 cell damage via ROS provoked by RAGE.
- myocardial infarction
- major adverse cardiac events
- reactive oxygen species
- ischemic injury
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology