Male Sex Hormone and Reduced Plakoglobin Jointly Impair Atrial Conduction and Cardiac Sodium Currents
June 2022
in “
bioRxiv (Cold Spring Harbor Laboratory)
”
androgenic anabolic steroids plakoglobin atrial conduction cardiac sodium currents arrhythmogenic right ventricular cardiomyopathy 5α-dihydrotestosterone DHT pro-hypertrophic transcripts fibrotic transcripts inflammatory transcripts sodium current density action potential amplitude Na v 1.5 clustering atrial electrical remodeling atrial myopathy desmosomal gene variants AAS
Studysummary This study found that anabolic steroid use combined with plakoglobin deficiency caused pathological atrial electrical remodeling in young male mice, suggesting a higher risk of atrial myopathy for males with desmosomal gene variants.
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The study investigated the effects of androgenic anabolic steroids (AAS) and reduced plakoglobin on atrial conduction and cardiac sodium currents, particularly in the context of arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical data from 146 ARVC patients showed a male preponderance and increased atrial arrhythmias. In an experimental setup, young adult male mice with heterozygous plakoglobin deficiency (Plako+/-) and wildtype (WT) littermates were exposed to 5α-dihydrotestosterone (DHT). The results indicated that DHT exposure led to atrial conduction slowing, decreased sodium current density, and reduced action potential amplitude in Plako+/- mice, but not in WT mice. This was associated with a reduction in Nav1.5 clustering in Plako+/- atrial cardiomyocytes. The findings suggested that AAS abuse, combined with plakoglobin deficiency, could lead to pathological atrial electrical remodeling, increasing the risk of atrial myopathy in males with desmosomal gene variants.
