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

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 Gullestad, Brage Høyem Amundsen, Geir Øystein Andersen, Mikael C. I. Karlsson, Malin Hagberg Thulin, Alessandro Camponeschi, Dana Trompet, Ola Hammarsten, Björn Redfors, Jan Borén, Elmir Omerovic, Malin C. Levin, Andrei S. Chagin, Tuva B. Dahl and Åsa Tivesten ()
Additional contact information
Elin Svedlund Eriksson: Sahlgrenska Academy at University of Gothenburg
Marta Lantero Rodriguez: Sahlgrenska Academy at University of Gothenburg
Bente Halvorsen: Oslo University Hospital Rikshospitalet
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
Camilla Huse: Oslo University Hospital Rikshospitalet
Thor Ueland: Oslo University Hospital Rikshospitalet
Pål Aukrust: Oslo University Hospital Rikshospitalet
Kaspar Broch: Oslo University Hospital Rikshospitalet
Lars Gullestad: University of Oslo
Brage Høyem Amundsen: Trondheim University Hospital
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
Dana Trompet: University of Gothenburg
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

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56217-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56217-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56217-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().