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Testosterone exacerbates neutrophilia and cardiac injury in myocardial infarction via actions in bone marrow

Author

Listed:
  • Elin Svedlund Eriksson

    (Sahlgrenska Academy at University of Gothenburg)

  • Marta Lantero Rodriguez

    (Sahlgrenska Academy at University of Gothenburg)

  • Bente Halvorsen

    (Oslo University Hospital Rikshospitalet
    University of Oslo)

  • Inger Johansson

    (Sahlgrenska Academy at University of Gothenburg)

  • Anna K. F. Mårtensson

    (Sahlgrenska Academy at University of Gothenburg)

  • Anna S. Wilhelmson

    (Sahlgrenska Academy at University of Gothenburg
    Copenhagen University Hospital - Rigshospitalet
    University of Copenhagen)

  • Camilla Huse

    (Oslo University Hospital Rikshospitalet
    University of Oslo
    Harvard Medical School)

  • Thor Ueland

    (Oslo University Hospital Rikshospitalet
    University of Oslo
    University Hospital of North Norway)

  • Pål Aukrust

    (Oslo University Hospital Rikshospitalet
    University of Oslo)

  • Kaspar Broch

    (Oslo University Hospital Rikshospitalet
    University of Oslo)

  • Lars Gullestad

    (University of Oslo
    Oslo University Hospital Rikshospitalet
    University of Oslo)

  • Brage Høyem Amundsen

    (Trondheim University Hospital
    Norwegian University of Science and Technology (NTNU))

  • Geir Øystein Andersen

    (Oslo University Hospital Ullevål)

  • Mikael C. I. Karlsson

    (Karolinska University Hospital)

  • Malin Hagberg Thulin

    (University of Gothenburg)

  • Alessandro Camponeschi

    (Sahlgrenska Academy at University of Gothenburg
    Sahlgrenska University Hospital)

  • Dana Trompet

    (University of Gothenburg
    Karolinska Institute)

  • Ola Hammarsten

    (University of Gothenburg)

  • Björn Redfors

    (Sahlgrenska Academy at University of Gothenburg)

  • Jan Borén

    (Sahlgrenska Academy at University of Gothenburg)

  • Elmir Omerovic

    (Sahlgrenska Academy at University of Gothenburg)

  • Malin C. Levin

    (Sahlgrenska Academy at University of Gothenburg)

  • Andrei S. Chagin

    (University of Gothenburg)

  • Tuva B. Dahl

    (Oslo University Hospital Rikshospitalet)

  • Åsa Tivesten

    (Sahlgrenska Academy at University of Gothenburg
    Region Västra Götaland)

Abstract

Men develop larger infarct sizes than women after a myocardial infarction (MI), but the mechanism underlying this sex difference is unknown. Here, we demonstrated that blood neutrophil counts post-MI were higher in male than female mice. Castration-induced testosterone deficiency reduced blood neutrophil counts to the level in females and increased survival post-MI. These effects were mimicked by Osterix-directed ablation of the androgen receptor in bone marrow (BM). Mechanistically, androgens downregulated the leukocyte retention factor CXCL12 in BM stromal cells. Post-hoc analysis of clinical trial data showed that neutrophilia was greater in men than women after reperfusion of first-time ST-elevation MI, and tocilizumab, an interleukin-6 receptor inhibitor, reduced blood neutrophil counts and infarct size to a greater extent in men than women. Our work reveals a previously unknown mechanism connecting testosterone with neutrophilia and MI injury via BM and identifies the importance of considering sex when developing anti-inflammatory strategies to treat MI.

Suggested Citation

  • Elin Svedlund Eriksson & Marta Lantero Rodriguez & Bente Halvorsen & Inger Johansson & Anna K. F. Mårtensson & Anna S. Wilhelmson & Camilla Huse & Thor Ueland & Pål Aukrust & Kaspar Broch & Lars Gulle, 2025. "Testosterone exacerbates neutrophilia and cardiac injury in myocardial infarction via actions in bone marrow," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56217-x
    DOI: 10.1038/s41467-025-56217-x
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    References listed on IDEAS

    as
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