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

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

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 bl...

Full description

Saved in:
Bibliographic Details
Main Authors: 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, Åsa Tivesten
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56217-x
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2041-1723

Similar Items