Horitani, Chavkin et al. report that the loss of the Y chromosome in macrophages from failing human hearts correlates with cardiac fibroblast activation and that the deficiency of a single Y chromosome gene, Uty, triggers an epigenetic rewiring in macrophages toward a profibrotic phenotype and increases cardiac fibrosis and dysfunction that can be prevented by TGFβ-neutralizing antibodies.
- Keita Horitani
- Nicholas W. Chavkin
- Kenneth Walsh