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Cited by 74Sex and Gender in HealthcareGenetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesCardiac electrophysiology and arrhythmias

Matters of the heart: Cellular sex differences

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Walker, Cierra J., Schroeder, Megan E., Aguado, Brian A., Anseth, Kristi S., Leinwand, Leslie A.·2021·Journal of Molecular and Cellular Cardiology
DOI 10.1016/j.yjmcc.2021.04.010PMC PMC8571046
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Abstract

Nearly all cardiovascular diseases show sexual dimorphisms in prevalence, presentation, and outcomes. Until recently, most clinical trials were carried out in males, and many animal studies either failed to identify the sex of the animals or combined data obtained from males and females. Cellular sex in the heart is relatively understudied and many studies fail to report the sex of the cells used for in vitro experiments. Moreover, in the small number of studies in which sex is reported, most of those studies use male cells. The observation that cells from males and females are inherently different is becoming increasingly clear - either due to acquired differences from hormones and other factors or due to intrinsic differences in genotype (XX or XY). Because of the likely contribution of cellular sex differences in cardiac health and disease, here, we explore differences in mammalian male and female cells in the heart, including the less-studied non-myocyte cell populations. We discuss how the heart's microenvironment impacts male and female cellular phenotypes and vice versa, including how secretory profiles are dependent on cellular sex, and how hormones contribute to sexually dimorphic phenotypes and cellular functions. Intracellular mechanisms that contribute to sex differences, including gene expression and epigenetic remodeling, are also described. Recent single-cell sequencing studies have revealed unexpected sex differences in the composition of cell types in the heart which we discuss. Finally, future recommendations for considering cellular sex differences in the design of bioengineered in vitro disease models of the heart are provided.

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Authors
Walker, C. J., Schroeder, M. E., Aguado, B. A., Anseth, K. S., & Leinwand, L. A.
Affiliations
University of Colorado Boulder (US)
Corresponding author
Leinwand, Leslie A.
ORCID
Venue
Journal of Molecular and Cellular Cardiology
Publisher
Elsevier BV
Published
2021-11
Volume
160
Pages
42-55
ISSN
0022-2828 (ISSN-L)
DOI
10.1016/j.yjmcc.2021.04.010
PMC
PMC8571046
OpenAlex
W3177175366
Cited by
74
References
208
Citations by year
2026: 10 · 2025: 16 · 2024: 12 · 2023: 12 · 2022: 19 · 2021: 5
FWCI
2.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Molecular and Cellular Cardiology (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (F31HL142223, K99 HL148542, R01 117138, R01 GM29090, R01 HL142935, RO1 HL132353, T32 HL007822)
  • Burroughs Wellcome Fund
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords
cardiovascular disease, sex hormones, sex chromosomes, cardiac microenvironment, epigenetic remodeling, gene expression, single-cell sequencing, in vitro disease model, sex bias in clinical trials
MeSH terms
Animals, Cardiovascular Diseases, Chromosomes, Extracellular Matrix, Female, Genotype, Heart, Humans, Male, Myocardium, Sex Factors, Gonadal Steroid Hormones, Transcriptome

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