Reduced Plakoglobin Increases the Risk of Sodium Current Defects and Atrial Conduction Abnormalities in Response to Androgenic Anabolic Steroid Abuse

February 2024 in “ The Journal of Physiology ”

Laura C. Sommerfeld, Andrew P. Holmes, Ting Yu, Christopher O’Shea, Deirdre M. Kavanagh, Jeremy A. Pike, Tom Wright, Fahima Syeda, Areej Aljehani, Tania Kew, Victor Roth Cardoso, S. Nashitha Kabir, Claire Hepburn, Priyanka Rajeev Menon, Sophie Broadway‐Stringer, Molly O’Reilly, Anika Witten, Lisa Fortmueller, Susanne Lutz, Alexandra Kulle, Georgios V. Gkoutos, Davor Pavlović, Wiebke Arlt, Gareth G. Lavery, Richard P. Steeds, Katja Gehmlich, Monika Stoll, Paulus Kirchhof, Larissa Fabritz

androgenic anabolic steroids plakoglobin arrhythmogenic right ventricular cardiomyopathy desmosomal gene defects 5α-dihydrotestosterone DHT atrial arrhythmias atrial conduction abnormalities sodium current defects AAS

TLDR Reduced plakoglobin and steroid abuse increase the risk of heart rhythm issues.

This study investigates the impact of androgenic anabolic steroids (AAS) on atrial conduction abnormalities, particularly in the context of arrhythmogenic right ventricular cardiomyopathy (ARVC), which is linked to desmosomal gene defects like reduced plakoglobin expression. Analyzing clinical records from 146 ARVC patients, the study found a higher prevalence of ARVC in males, who also exhibited increased atrial arrhythmias and P wave changes. In an experimental setup, young male mice with reduced plakoglobin expression showed exacerbated atrial electrical remodeling when exposed to 5α-dihydrotestosterone (DHT), including P wave abnormalities, slowed atrial conduction, and sodium current depletion. The findings suggest that AAS use, combined with plakoglobin deficiency, heightens the risk of atrial arrhythmias, particularly in males with desmosomal gene variants.