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Sex-chromosome mechanisms in cardiac development and disease

Nature Cardiovascular Research volume 2, pages 340–350 (2023)Cite this article

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Abstract

Many human diseases, including cardiovascular disease, show differences between men and women in pathology and treatment outcomes. In the case of cardiac disease, sex differences are exemplified by differences in the frequency of specific types of congenital and adult-onset heart disease. Clinical studies have suggested that gonadal hormones are a factor in sex bias. However, recent research has shown that gene and protein networks under non-hormonal control also account for cardiac sex differences. In this Review, we describe the sex-chromosome pathways that lead to sex differences in the development and function of the heart and highlight how these findings affect future care and treatment of cardiac disease.

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Fig. 1: The FCG mouse model.
Fig. 2: XY* mouse models.
Fig. 3: In mice, cardiac tissue is specified and determined, and forms a beating heart, before the differentiation of bipotential gonads into a testis or ovary.
Fig. 4: Genes or genes coding for proteins on the X chromosome that display male–female differences in cardiac expression.
Fig. 5: Potential mechanisms of post-transcriptional regulation associated with cardiac male–female sex differences.

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Acknowledgements

We thank the members of the Conlon Lab for editing and proofing and A. Scialdone for her help with editing. We thank the three reviewers for contributing to the external peer review. We regret that we could not recognize all pertinent research in the field and contributions from investigators owing to space constraints. This work was supported by the grants R01HL156424 NIH/NHLBI to F.L.C. A.P.A. was supported by OD030496, HD1002989, HL131182 and DK083561.

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  1. Departments of Biology and Genetics, McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC, USA

    Frank L. Conlon

  2. Department of Integrative Biology & Physiology, University of California, Los Angeles, CA, USA

    Arthur P. Arnold

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F.L.C. and A.P.A. wrote and edited the manuscript.

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Conlon, F.L., Arnold, A.P. Sex-chromosome mechanisms in cardiac development and disease. Nat Cardiovasc Res 2, 340–350 (2023). https://doi.org/10.1038/s44161-023-00256-4

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