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
TLDR Male hormones and reduced plakoglobin can impair heart electrical function and increase arrhythmia risk in males.
The study investigated the effects of androgenic anabolic steroids (AAS) and reduced plakoglobin on atrial conduction and cardiac sodium currents, focusing on young male subjects. Analysis of 146 patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) showed a male preponderance and increased atrial arrhythmias. In a mouse model, young adult male mice with heterozygous plakoglobin deficiency (Plako +/-) and wildtype (WT) littermates were exposed to 5α-dihydrotestosterone (DHT). DHT exposure led to increased expression of pro-hypertrophic, fibrotic, and inflammatory transcripts, atrial conduction slowing, decreased sodium current density, and reduced action potential amplitude in Plako +/- mice, but not in WT mice. Super-resolution microscopy showed reduced Na v 1.5 clustering in Plako +/- atrial cardiomyocytes. The findings suggested that AAS abuse, combined with plakoglobin deficiency, could lead to pathological atrial electrical remodeling and increased risk of atrial myopathy in males with desmosomal gene variants.
