The AP-1 transcription factor Fosl-2 drives cardiac fibrosis and arrhythmias under immunofibrotic conditions.

ABSTRACT: Fibrotic changes in the myocardium and cardiac arrhythmias represent fatal complications in systemic sclerosis (SSc), however the underlying mechanisms remain elusive. Mice overexpressing transcription factor Fosl-2 (Fosl-2^tg) represent animal model of SSc. Fosl-2^tg mice showed interstitial cardiac fibrosis, disorganized connexin-43/40 in intercalated discs and deregulated expression of genes controlling conduction system, and developed higher heart rate (HR), prolonged QT intervals, arrhythmias with prevalence of premature ventricular contractions, ventricular tachycardias, II-degree atrio-ventricular blocks and reduced HR variability. Following stimulation with isoproterenol Fosl-2^tg mice showed impaired HR response. In contrast to Fosl-2^tg, im

SUBMITTER: Stellato M 

PROVIDER: S-EPMC9911788 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature