Testosterone exacerbates neutrophilia and cardiac injury in myocardial infarction via actions in bone marrow.
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Svedlund Eriksson E, Lantero Rodriguez M, Halvorsen B, Johansson I, Mårtensson AKF, Wilhelmson AS, Huse C, Ueland T, Aukrust P, Broch K, Gullestad L, Amundsen BH, Andersen GØ, Karlsson MCI, Hagberg Thulin M, Camponeschi A, Trompet D, Hammarsten O, Redfors B, Borén J, Omerovic E, Levin MC, Chagin AS, Dahl TB, Tivesten Å
Nat Commun 16 (1) 1142 [2025-02-05; online 2025-02-05]
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.
Clinical Genomics Gothenburg [Service]
PubMed 39910039
DOI 10.1038/s41467-025-56217-x
Crossref 10.1038/s41467-025-56217-x
pmc: PMC11799197
pii: 10.1038/s41467-025-56217-x