%0 Journal Article
%A Annamalai, Karthika
%A Dilliker, Soniya
%A Buchholz, Eric
%A Castro-Hernández, Ricardo
%A Panyam, Nikita
%A Pommeranz, Alessa
%A Wiederhake, Pascal
%A Wery von Limont, Nelly
%A Hempel, Nina
%A Ebner, Verena
%A Swarnkar, Surabhi
%A Mohamed, Belal A
%A Streckfuss-Bömeke, Katrin
%A Steffens, Sabine
%A Herzig, Stephan
%A Ebert, Antje
%A Fischer, Andre
%A Toischer, Karl
%T Deregulation of m6A-RNA methylation impairs adaptive hypertrophic response and drives maladaptation via mTORC1-S6K1-hyperactivation and autophagy impairment.
%J Cell communication and signaling
%V 23
%N 1
%@ 1478-811X
%C London
%I Biomed Central
%M DZNE-2025-01373
%P 522
%D 2025
%X Pressure overload first leads to compensated hypertrophy and secondary to heart failure. m6A-RNA methylation is a fast process for the adaptation of cell composition. m6A-RNA-methylation is regulated by the demethylase, fat mass and obesity-associated protein (FTO), and FTO protein levels are diminished in heart failure. Cardiomyocyte-specific FTO-transgenic/knockout-mice have shown the relevance of FTO in pressure overload remodeling. However, its functional downstream regulatory mechanisms are still unclear. In this study, we discover the harmful signaling pathways that are triggered by m6A imbalance and FTO loss, which eventually lead to adverse cardiac remodeling and heart failure.FTOcKO animals were generated by crossing FTOfl/fl mice with [Formula: see text]-MHC Cre mice using Cre-lox system. Control and the FTOcKO animals groups were subjected to TAC (transverse aortic constriction) surgery. Echocardiography was performed 1-week post-TAC surgery. MeRIP (m6A RNA immunoprecipitation) sequencing was performed from the heart tissues of mice after one week TAC surgery. Additionally, the mechanistical interrelation between the signaling pathways during FTO loss and adverse cardiac remodeling were investigated in human iPS-CMs (hiPS-CMs).One week post-TAC surgery, FTOcKO mice showed impaired cardiac function (EF: CreC TAC (45
%K Apoptosis (Other)
%K Atrophy (Other)
%K Cardiac hypertrophy (Other)
%K Mouse (Other)
%K N6-methyladenosine (Other)
%K Pathological remodeling (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41327199
%2 pmc:PMC12690826
%R 10.1186/s12964-025-02509-0
%U https://pub.dzne.de/record/282912