Deficiency of Testosterone Associates with the Substrate of Atrial Fibrillation in the Rat Model
Abstract
Background: Since the prevalence of atrial fibrillation (AF) increases progressively with aging, especially in men, we hypothesized that testosterone might affect the occurrence of AF. Methods and Results: We examined the electrophysiological properties of the atria in isolated‐perfused hearts of sham‐operated male (SM), female (SF), orchiectomized male with and without administration of testosterone (ORCH‐T and ORCH), and ovariectomized female (OVX) Sprague‐Dawley rats. An electrophysiological study revealed that repetitive atrial responses induced by electrical stimuli significantly increased in ORCH rats without changes in other electrophysiological properties and were abolished by administration of testosterone. To investigate the underlying mechanisms, we evaluated the expression level of calcium‐handling proteins. In ORCH rats, the immunoreactive protein level of ryanodine receptor type 2 (RyR2) and sodium–calcium exchanger significantly increased as compared with SM and ORCH‐T rats without alterations in the level of FK506‐binding protein (FKBP12.6), sarcoendoplasmic reticulum Ca‐ATPase, and phospholamban. Immunoprecipitation analysis demonstrated decreased binding of FKBP12.6 to RyR2 in ORCH rats, which was prevented by testosterone. In contrast, the expression levels of these proteins showed no significant differences between SF and OVX rats. Conclusion: Deficiency of testosterone was arrhythmogenic in rat atria possibly through less binding of FKBP12.6 to RyR2, which could induce feasible calcium leakage from the sarcoendoplasmic reticulum. These results would explain, at least in part, the increase in the prevalence of AF in accordance with the decline of testosterone particularly in elderly men.
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Data from the REGARDS and Atherosclerosis Risk in Communities studies indicated that the association between AF and myocardial infarction was greater in women than in men.
“Data from the REGARDS and Atherosclerosis Risk in Communities studies indicated that the association between AF and MI was greater in women than in men.104,105”
From Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis (2016) · cites this paper as [104]
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Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis
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- Authors
- TSUNEDA, T., YAMASHITA, T., KATO, T., SEKIGUCHI, A., SAGARA, K., SAWADA, H., AIZAWA, T., FU, L., FUJIKI, A., & INOUE, H.
- Affiliations
- Cardiovascular Institute Hospital (JP)
- University of Toyama (JP)
- Corresponding author
- TSUNEDA, TAKAYUKI
- Venue
- Journal of Cardiovascular Electrophysiology
- Publisher
- Wiley
- Published
- 2009-08-26
- Volume
- 20
- Issue
- 9
- Pages
- 1055-1060
- ISSN
- 1045-3873 (ISSN-L)
- 1540-8167
- OpenAlex
- W1998276573
- Cited by
- 49
- References
- 25
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 1
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cardiovascular Electrophysiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Keywords
- androgen deficiency, atrial fibrillation, orchiectomy, calcium handling, RyR2, FKBP12.6, calcium leak, Na+/Ca2+ exchanger, arrhythmogenesis, aging, sex differences
- MeSH terms
- Animals, Atrial Fibrillation, Disease Models, Animal, Female, Humans, Male, Testosterone, Rats, Sprague-Dawley, Rats
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