期刊
CARDIOVASCULAR RESEARCH
卷 117, 期 10, 页码 2252-2261出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvaa265
关键词
Sex differences; Cardiac cell composition; Cardiac fibroblast; Cardiac macrophage
资金
- National Health and Medical Research Council [GNT1188503]
- Jackson Laboratory Cancer Center Core grant
- Leducq Foundation Transatlantic Network of Excellence in Cardiac Research [P30 CA034196]
- State Government of Victoria
- Australian Government
This study reveals that the cellular composition of mouse heart is hormone-dependent, with distinct landscapes in females and males that are plastic and can be rapidly modulated by endocrine factors. These findings have implications for therapeutic strategies targeting cardiac cellular heterogeneity and highlight the importance of biological sex in studies of cardiac physiology and stress responses.
Aims Sex differences have been consistently identified in cardiac physiology and incidence of cardiac disease. However, the underlying biological causes for the differences remain unclear. We sought to characterize the cardiac non-myocyte cellular landscape in female and male hearts to determine whether cellular proportion of the heart is sex-dependent and whether endocrine factors modulate the cardiac cell proportions. Methods and results Utilizing high-dimensional flow cytometry and immunofluorescence imaging, we found significant sex-specific differences in cellular composition of the heart in adult and juvenile mice, that develops postnatally. Removal of systemic gonadal hormones by gonadectomy results in rapid sex-specific changes in cardiac non-myocyte cellular proportions including alteration in resident mesenchymal cell and leucocyte populations, indicating gonadal hormones and their downstream targets regulate cardiac cellular composition. The ectopic reintroduction of oestrogen and testosterone to female and male mice, respectively, reverses many of these gonadectomy-induced compositional changes. Conclusion This work shows that the constituent cell types of the mouse heart are hormone-dependent and that the cardiac cellular landscapes are distinct in females and males, remain plastic, and can be rapidly modulated by endocrine factors. These observations have implications for strategies aiming to therapeutically alter cardiac cellular heterogeneity and underscore the importance of considering biological sex for studies examining cardiac physiology and stress responses.
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