Computational modeling identifies protective mechanisms of estrogen and testosterone against atrial fibrosis

American Journal of Physiology-Heart and Circulatory Physiology 2026 Open access

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Authors: Najme Khorasani, Stefano Morotti, Jeffrey J. Saucerman, Dobromir Dobrev, Eleonora Grandi
DOI: 10.1152/ajpheart.00249.2026
Cited by: 1
References: 138

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.

Fields of Study & Subjects

Atrial Fibrillation Management and Outcomes Cardiac Fibrosis and Remodeling Cardiovascular Function and Risk Factors

Publication details

Journal / source
American Journal of Physiology-Heart and Circulatory Physiology
Publisher
American Physiological Society
Volume
331
Issue
2
Pages
H407–H422
Publication date
16 June 2026
Language
EN