IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-56978-5.html
   My bibliography  Save this article

S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axis

Author

Listed:
  • Xi Zhang

    (General Hospital of Northern Theater Command)

  • Haixu Song

    (General Hospital of Northern Theater Command)

  • Dan Liu

    (General Hospital of Northern Theater Command)

  • Yi Cai

    (General Hospital of Northern Theater Command)

  • Ziqi Liu

    (General Hospital of Northern Theater Command)

  • Xiaolin Zhang

    (General Hospital of Northern Theater Command)

  • Xiaojie Zhao

    (General Hospital of Northern Theater Command)

  • Yan Zhang

    (General Hospital of Northern Theater Command)

  • Quanmin Jing

    (General Hospital of Northern Theater Command)

  • Chenghui Yan

    (General Hospital of Northern Theater Command)

  • Yaling Han

    (General Hospital of Northern Theater Command)

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.

Suggested Citation

  • Xi Zhang & Haixu Song & Dan Liu & Yi Cai & Ziqi Liu & Xiaolin Zhang & Xiaojie Zhao & Yan Zhang & Quanmin Jing & Chenghui Yan & Yaling Han, 2025. "S100A12 triggers NETosis to aggravate myocardial infarction injury via the Annexin A5-calcium axis," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56978-5
    DOI: 10.1038/s41467-025-56978-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-56978-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-56978-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56978-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.