Association of serum HMGB2 level with MACE at 1 mo of myocardial infarction: Aggravation of myocardial ischemic injury in rats by HMGB2 via ROS
| Autor: | Ying Chen, Ping Yang, Zhu Hui Liu, Dao Peng Dai, Xiao Qun Wang, Qi Zhang, Wen Qi Pan, Yue Hua Fang, Feng Hua Ding, Yu Hu He, Weifeng Shen, Ying Shen, Ke Yang, Ling Jie Wang, Man Li, Lin Lu, Xiao Xiang Yan, Rui Yan Zhang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Glycation End Products Advanced Male Physiology Myocardial Ischemia Apoptosis 030204 cardiovascular system & hematology Rats Sprague-Dawley 0302 clinical medicine Phagosomes Myocardial infarction NADPH oxidase biology Ischemic injury Heart Stroke volume Middle Aged cardiovascular system Cardiology Female medicine.symptom Cardiology and Cardiovascular Medicine medicine.medical_specialty Inflammation HMGB2 Cell Line 03 medical and health sciences Physiology (medical) Internal medicine medicine Animals HMGB2 Protein Humans cardiovascular diseases Aged business.industry Myocardium Acetophenones NADPH Oxidases Stroke Volume medicine.disease Surgery Rats 030104 developmental biology biology.protein ST Elevation Myocardial Infarction business Reactive Oxygen Species Mace |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 312(3) |
| ISSN: | 1522-1539 |
| Popis: | 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. 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 coadministration of the NADPH oxidase inhibitor apocynin. After 72 h, pathological, 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 coadministration of apocynin or knock down of receptor for advanced glycation end products (RAGE). In conclusion, increased serum HMGB2 levels are associated with MI severity and MACE at 1 mo. HMGB2 promotes myocardial ischemic injury in rats and hypoxic H9C2 cell damage via ROS provoked by RAGE.NEW & NOTEWORTHY We demonstrate that serum high-mobility group box 2 is associated with major adverse cardiac events at 1 mo in myocardial infarction patients. Mechanistically, high-mobility group box 2 promotes reactive oxygen species production via receptor for advanced glycation end products signaling in ischemic myocardium, thereby aggravating cell apoptosis, inflammation, and autophagosome clearance impairment. This study reveals that high-mobility group box 2 is a novel factor enhancing ischemic injury in myocardial infarction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|