Document Type

Article

Publication Date

8-29-2021

Publication Title

Cardiovascular research

JAX Source

Cardiovasc Res 2021 Aug 29; 117(10):2252-2262

Volume

117

Issue

10

First Page

2252

Last Page

2262

ISSN

1755-3245

PMID

32941598

DOI

https://doi.org/10.1093/cvr/cvaa265

Grant

CA034196, GMT1188503

Abstract

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.

Comments

attached copy is from PMC

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