title: Association of serum HMGB2 level with MACE at 1 mo of myocardial infarction: Aggravation of myocardial ischemic injury in rats by HMGB2 via ROS.
abstract: 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 & NOTEWORTHYWe 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.
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.
authors.forename: Zhu Hui
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.
authors.forename: Dao Peng
authors.initials: DP
authors.lastname: Dai
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.
authors.forename: Feng Hua
authors.initials: FH
authors.lastname: Ding
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.
authors.forename: Wen Qi
authors.initials: WQ
authors.lastname: Pan
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.
authors.forename: Yue Hua
authors.initials: YH
authors.lastname: Fang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.|Institute of Cardiovascular Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xiao Qun
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.|Institute of Cardiovascular Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Ling Jie
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.|Institute of Cardiovascular Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xiao Xiang
authors.initials: XX
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.
authors.forename: Yu Hu
authors.initials: YH
authors.lastname: He
authors.affiliation: Institute of Cardiovascular Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.
authors.forename: Rui Yan
authors.initials: RY
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.|Institute of Cardiovascular Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Wei Feng
authors.initials: WF
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; and lulin_1965@163.com.|Institute of Cardiovascular Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000368:Aged; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D024261:HMGB2 Protein / Q000097:blood* / Q000235:genetics / Q000633:toxicity*; D006321:Heart / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood*; D009206:Myocardium / Q000473:pathology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D010588:Phagosomes; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000072657:ST Elevation Myocardial Infarction / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D013318:Stroke Volume
chemical_list: D000098:Acetophenones; D017127:Glycation End Products, Advanced; D024261:HMGB2 Protein; D017382:Reactive Oxygen Species; C056165:acetovanillone; D019255:NADPH Oxidases
keywords: high-mobility group box 2; ischemic injury; major adverse cardiac events; myocardial infraction; reactive oxygen species