Tankyrase inhibition attenuates cardiac dilatation and dysfunction in ischemic heart failure

Background and Aims : Hyperactive poly(ADP-ribose) polymerases (PARP) promote ischemic heart failure (IHF) after myocardial infarction (MI). However, the role of Tankyrases (TNKSs), members PARP family, in progression IHF remains unknown. We aimed to explore TNKSs pathophysiological process therapeutic potential TNKS inhibition for IHF.Methods: Cardiac samples from patients MI rats were employed investigate expression activation TNKSs. Isoproterenol-induced HF zebrafish model was utilized a cardioprotective effect inhibition.Results: demonstrate significant augmentation TNKS2 DICER, concomitant upregulation miR-34a-5p miR-21-5p myocardium patients. further reveal that augments TNKS1 infarct border areas at 1 week 4 weeks post-MI rat. stimulates activity triggers Wnt/β-catenin signalling area onward. induces an abundant distribution subset non-cardiomyocytes with enhanced progenitor cardiomyocytes displaying cell shrinkage sarcomere disorganization Importantly, we show XAV939, TNKS-specific inhibitor, protects against ventricular dilatation cardiac dysfunction isoproterenol-induced zebrafish. Concomitantly, abrogates overactivation dysregulation miR-19b-3p, miR-181a-5p, induced by isoproterenol.Conclusions: Our study unravels novel pathogenesis via modulating miRNAs signalling, highlighting pharmacotherapeutic inhibition. IHF. Methods: Results: isoproterenol. Conclusions: