S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axis.
Xi Zhang, Haixu Song, Dan Liu, Yi Cai, Ziqi Liu, Xiaolin Zhang, Xiaojie Zhao, Yan Zhang, Quanmin Jing, Chenghui Yan, Yaling Han
Author Information
Xi Zhang: State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, China.
Haixu Song: State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, China.
Dan Liu: State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, China.
Yi Cai: State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, China.
Ziqi Liu: State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, China.
Xiaolin Zhang: State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, China.
Xiaojie Zhao: State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, China.
Yan Zhang: State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, China.
Quanmin Jing: State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, China.
Chenghui Yan: State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, China. yanch1029@163.com. ORCID
Yaling Han: State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, China. hanyaling@163.net. ORCID
Neutrophil extracellular traps (NETs) play a critical role in acute myocardial infarction (AMI) and the externalization of S100 family members. Here, we show the effects of S100A12 on NETs formation and myocardial injury following AMI. S100A12 expression increases rapidly in neutrophils and peaks on day 1 after AMI, promoting NETs production and exacerbating myocardial injury. DNase I, an inhibitor of NETs, reduces apoptosis of cardiomyocytes induced by S100A12. Mechanistically, the interaction of S100A12 and Annexin A5 (ANXA5) enhances calcium influx and promotes NETs formation. Blockage of ANXA5 effectively attenuates heart function impairment after AMI. Finally, we show that plasma S100A12 levels correlate with dsDNA concentration, and this correlation is associated with an increased risk of all-cause mortality during the 1-year follow-up of AMI patients. These findings, derived from male mice, reveal the S100A12-ANXA5-calcium influx axis as a potential therapeutic target and biomarker for AMI.
