S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axis
Abstract 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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56978-5 |
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| author | Xi Zhang Haixu Song Dan Liu Yi Cai Ziqi Liu Xiaolin Zhang Xiaojie Zhao Yan Zhang Quanmin Jing Chenghui Yan Yaling Han |
| author_facet | Xi Zhang Haixu Song Dan Liu Yi Cai Ziqi Liu Xiaolin Zhang Xiaojie Zhao Yan Zhang Quanmin Jing Chenghui Yan Yaling Han |
| author_sort | Xi Zhang |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-3fe711a14bb346c9889d59f6d95657a3 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-3fe711a14bb346c9889d59f6d95657a32025-08-20T03:10:49ZengNature PortfolioNature Communications2041-17232025-02-0116111610.1038/s41467-025-56978-5S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axisXi Zhang0Haixu Song1Dan Liu2Yi Cai3Ziqi Liu4Xiaolin Zhang5Xiaojie Zhao6Yan Zhang7Quanmin Jing8Chenghui Yan9Yaling Han10State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater CommandState Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater CommandAbstract 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.https://doi.org/10.1038/s41467-025-56978-5 |
| spellingShingle | Xi Zhang Haixu Song Dan Liu Yi Cai Ziqi Liu Xiaolin Zhang Xiaojie Zhao Yan Zhang Quanmin Jing Chenghui Yan Yaling Han S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axis Nature Communications |
| title | S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axis |
| title_full | S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axis |
| title_fullStr | S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axis |
| title_full_unstemmed | S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axis |
| title_short | S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axis |
| title_sort | s100a12 triggers netosis to aggravate myocardial infarction injury via the annexin a5 calcium axis |
| url | https://doi.org/10.1038/s41467-025-56978-5 |
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