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Sex-Related Effects on Cardiac Development and Disease
Georgios Siokatas1, Ioanna Papatheodorou1, Angeliki Daiou1
1School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Insights
Sex determination factors influence cardiovascular disease (CVD) development and treatment. Understanding the "sex determination-heart axis" may reveal new cardiac repair and regeneration strategies.
Area of Science:
- Cardiovascular Science
- Endocrinology
- Genetics
Background:
- Cardiovascular diseases (CVD) are a major global health burden.
- Sex-based differences exist in CVD epidemiology and pathophysiology.
- Sex determination factors may play a crucial role in heart health.
Purpose of the Study:
- To review the current understanding of the "sex determination-heart axis".
- To identify knowledge gaps in sex-specific heart development, aging, and disease.
- To explore therapeutic potential for cardiac regeneration and repair.
Main Methods:
- Literature review focusing on sex determination and cardiovascular manifestations.
- Analysis of cardiovascular aspects in human sex determination disorders (e.g., Turner, Klinefelter syndromes).
- Comparison of cardiac regenerative potential across species with varying sexual phenotypes.
Main Results:
- Distinct cardiovascular characteristics are observed between males and females with CVD.
- Abnormal sex determination is linked to specific cardiovascular issues.
- Sex-biased cardiac repair mechanisms, influenced by hormones like 17β-estradiol, are evident.
Conclusions:
- Elucidating the "sex determination-heart axis" is critical for understanding CVD.
- Sex-specific factors impact cardiac aging, disease, and regeneration.
- Targeting this axis may unlock novel therapeutic avenues for heart repair.
Abstract:
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality. Interestingly, male and female patients with CVD exhibit distinct epidemiological and pathophysiological characteristics, implying a potentially important role for primary and secondary sex determination factors in heart development, aging, disease and therapeutic responses. Here, we provide a concise review of the field and discuss current gaps in knowledge as a step towards elucidating the "sex determination-heart axis". We specifically focus on cardiovascular manifestations of abnormal sex determination in humans, such as in Turner and Klinefelter syndromes, as well as on the differences in cardiac regenerative potential between species with plastic and non-plastic sexual phenotypes. Sex-biased cardiac repair mechanisms are also discussed with a focus on the role of the steroid hormone 17β-estradiol. Understanding the "sex determination-heart axis" may offer new therapeutic possibilities for enhanced cardiac regeneration and/or repair post-injury.