Xi Zhang, Haixu Song, Dan Liu, Yi Cai, Ziqi Liu, Xiaolin Zhang, Xiaojie Zhao, Yan Zhang, Quanmin Jing, Chenghui Yan, Yaling Han
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S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axis
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.
期刊介绍：
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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