Computational modeling identifies protective mechanisms of estrogen and testosterone against atrial fibrosis
Year: 2026
Type: article
Abstract: We developed a sex-informed computational model of atrial Fb signaling and used it to identify the mechanistic basis of sex hormone-dependent antifibrotic effects. TS acted primarily through Smad3, whereas ROS-JNK signaling emerged as a dominant mediator of E2-dependent antifibrotic protection, largely through coordinated feedback regulation. These findings offer hormone-specific regulatory nodes that may serve as a potential target for durable antifibrotic therapy in AF across sex and age.
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G1095996902, G1532094542, G1868849738, Revealing key mechanisms of AF-associated fibrosis using network modeling, G3480172209, G3507403196, G363383531, GRK 2989: Distinkte zelluläre Interfaces im reperfundierten akuten Myokardinfarkt, G4865840433, G5295698330, G5526700752, G577373819, G6051119450, G6728121229, G686560780, Phosphodiesterase 1 (PDE1) Regulation of Myocardial Calcium and Function, The Role of Gasdermin-D/Interleukin-1 Nexus in Atrial Arrhythmogenesis, FKBP5 AND CARDIAC ARRHYTHMOGENESIS, Calcium Driven Fibroblast Dysregulation in Human Atrial Profibrotic Remodeling
OpenAlex ID: W7164910449