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Kcne4 deletion sex-specifically predisposes to cardiac arrhythmia via testosterone-dependent impairment of RISK/SAFE pathway induction in aged mice.


ABSTRACT: Sudden cardiac death (SCD) is associated with both electrical and ischemic substrates, and is a major cause of ischemic heart disease mortality worldwide. Male sex predisposes to SCD but the underlying mechanisms are incompletely understood. KCNE4, a cardiac arrhythmia-associated potassium channel ?-subunit, is upregulated by 5?-dihydrotestosterone (DHT). Thus, ventricular Kcne4 expression is low in young adult female mice, but high in males and postmenopausal (12+ months) females. Despite causing a sex-independent electrical substrate at 13 months of age (22% QT prolongation in both males and females; P?

SUBMITTER: Hu Z 

PROVIDER: S-EPMC5974354 | BioStudies | 2018-01-01T00:00:00Z

SECONDARY ACCESSION(S): rs697829

REPOSITORIES: biostudies

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