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 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 coun

SUBMITTER: Svedlund Eriksson E 

PROVIDER: S-EPMC11799197 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature