| Autor: |
Laura C. Sommerfeld, Andrew P. Holmes, Ting Y. Yu, Christopher O’Shea, Deirdre M. Kavanagh, Jeremy M. Pike, Thomas Wright, Fahima Syeda, Areej Aljehani, Tania Kew, Victor R. Cardoso, S. Nashitha Kabir, Claire Hepburn, Priyanka M. Menon, Sophie Broadway-Stringer, Molly O’Reilly, Anika Witten, Lisa Fortmueller, Susanne Lutz, Alexandra Kulle, Georgios V. Gkoutos, Davor Pavlovic, Wiebke Arlt, Gareth G. Lavery, Richard Steeds, Katja Gehmlich, Monika Stoll, Paulus Kirchhof, Larissa Fabritz |
| Rok vydání: |
2022 |
| Popis: |
Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex associates with earlier manifestation of common and rare cardiac conditions including atrial fibrillation and arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical data suggest an atrial involvement in ARVC. The disease is caused by desmosomal gene defects such as reduced plakoglobin expression. Analysis of clinical records from 146 ARVC patients identified male preponderance and increased prevalence of atrial arrhythmias in patients with definite ARVC. Definite patients displayed ECG changes suggesting atrial remodelling. To study mechanisms of atrial remodelling due to desmosomal vulnerability and AAS, young adult male mice, heterozygously deficient for plakoglobin (Plako+/-) and wildtype (WT) littermates, were chronically exposed to 5α-dihydrotestosterone (DHT) or placebo. DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. DHT caused atrial conduction slowing, decreased peak sodium current density, reduced action potential amplitude and lowered the peak depolarisation rate in Plako+/- but not WT atria. Super-resolution microscopy revealed a reduction in Nav1.5 clustering in Plako+/- atrial cardiomyocytes following DHT exposure. These data reveal that AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. AAS abuse may increase the risk of atrial myopathy in males with desmosomal gene variants. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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