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Connexin Lateralization Contributes to Male Susceptibility to Atrial Fibrillation
Simon Thibault1,2, Anh-Tuan Ton1,2, François Huynh1,2
1Research Center, Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.
International Journal of Molecular Sciences
|September 23, 2022
Summary
Men have a higher risk of atrial fibrillation (AF). Male mice show increased connexin lateralization and larger atria, contributing to AF susceptibility. Androgen reduction via orchiectomy mitigated these AF risks.
Area of Science:
- Cardiovascular Research
- Electrophysiology
- Endocrinology
Background:
- Men exhibit a higher incidence of atrial fibrillation (AF) compared to women.
- The underlying mechanisms for this sex disparity in AF risk remain unclear.
Purpose of the Study:
- To investigate sex-based differences in atrial electrical and structural properties in mice.
- To explore the role of sex hormones in AF susceptibility.
Main Methods:
- Compared atrial electrophysiology and connexin distribution in male and female mice.
- Utilized immunofluorescence and mRNA expression analysis.
- Assessed AF susceptibility following orchiectomy (ORC) and ovariectomy (OVX).
Main Results:
- Male atrial myocytes displayed greater lateralization of connexins 40 and 43 compared to females.
- Males had significantly higher atrial mass and larger atrial myocyte dimensions.
- Orchiectomy abolished sex differences in AF susceptibility by reducing connexin lateralization and myocyte size.
Conclusions:
- Pre-age-related remodeling, male mice possess structural and electrical atrial characteristics predisposing them to AF.
- Androgens appear to play a role in AF susceptibility through effects on connexin lateralization and myocyte size.
- These sex-specific atrial substrates may explain the higher prevalence of AF in males.
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