Calcineurin-NFAT dynamics correspond to cardiac remodeling during aortic banding and debanding, mimicking aortic valve replacement

Aortic valve stenosis (AS) is a major health problem. Extensive myocardial remodeling increases operative risk and might lead to incomplete reverse with persistent symptoms after aortic replacement (AVR); this makes the optimal timing of AVR clinical challenge. The pathogenesis behind unclear. Central among signaling pathways in heart pro-hypertrophic Ca 2+ -activated calcineurin its downstream nuclear factor activated T-cell (NFATc1-c4) transcription factors. We investigated calcineurin-NFATc dynamics patient mouse hearts during remodeling. Myocardial biopsies were obtained from AS patients left ventricles harvested mice subjected banding (AB) debanding (DB). transcript protein NFATc-responsive gene regulator 1-4 (RCAN1-4) luciferase activity NFAT-luciferase used as read-outs for activity. Calcineurin-NFATc activation was sustained through AB 24 h 18 weeks elevated patients. All four NFATc isoforms AS, while NFATc4 persistently chronic mice. NFAT remained reversible when 1 week’s followed by week's DB accompanied functional improvement. However, week 4 weeks, not reversed. In conclusion, calcineurin-NFAT correspond cardiac experimental DB. Our data suggest that attenuation important outcomes AS.