Your browser doesn't support javascript.
loading
Tankyrase Inhibition Attenuates Cardiac Dilatation and Dysfunction in Ischemic Heart Failure.
Wang, Hong; Segersvärd, Heli; Siren, Juuso; Perttunen, Sanni; Immonen, Katariina; Kosonen, Riikka; Chen, Yu-Chia; Tolva, Johanna; Laivuori, Mirjami; Mäyränpää, Mikko I; Kovanen, Petri T; Sinisalo, Juha; Laine, Mika; Tikkanen, Ilkka; Lakkisto, Päivi.
Afiliação
  • Wang H; Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland.
  • Segersvärd H; Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland.
  • Siren J; Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland.
  • Perttunen S; Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland.
  • Immonen K; Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland.
  • Kosonen R; Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland.
  • Chen YC; Zebrafish Unit, HiLIFE and Department of Anatomy, University of Helsinki, 00014 Helsinki, Finland.
  • Tolva J; Transplantation Laboratory, Department of Pathology, University of Helsinki, 00014 Helsinki, Finland.
  • Laivuori M; Department of Vascular Surgery, Abdominal Center, Helsinki University Hospital and University of Helsinki, 00014 Helsinki, Finland.
  • Mäyränpää MI; Department of Pathology, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland.
  • Kovanen PT; Atherosclerosis Research Laboratory, Wihuri Research Institute, 00290 Helsinki, Finland.
  • Sinisalo J; Heart and Lung Center, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland.
  • Laine M; Heart and Lung Center, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland.
  • Tikkanen I; Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland.
  • Lakkisto P; Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland.
Int J Mol Sci ; 23(17)2022 Sep 02.
Article em En | MEDLINE | ID: mdl-36077457
Hyperactive poly(ADP-ribose) polymerases (PARP) promote ischemic heart failure (IHF) after myocardial infarction (MI). However, the role of tankyrases (TNKSs), members of the PARP family, in pathogenesis of IHF remains unknown. We investigated the expression and activation of TNKSs in myocardium of IHF patients and MI rats. We explored the cardioprotective effect of TNKS inhibition in an isoproterenol-induced zebrafish HF model. In IHF patients, we observed elevated TNKS2 and DICER and concomitant upregulation of miR-34a-5p and miR-21-5p in non-infarcted myocardium. In a rat MI model, we found augmented TNKS2 and DICER in the border and infarct areas at the early stage of post-MI. We also observed consistently increased TNKS1 in the border and infarct areas and destabilized AXIN in the infarct area from 4 weeks onward, which in turn triggered Wnt/ß-catenin signaling. In an isoproterenol-induced HF zebrafish model, inhibition of TNKS activity with XAV939, a TNKSs-specific inhibitor, protected against ventricular dilatation and cardiac dysfunction and abrogated overactivation of Wnt/ß-catenin signaling and dysregulation of miR-34a-5p induced by isoproterenol. Our study unravels a potential role of TNKSs in the pathogenesis of IHF by regulating Wnt/ß-catenin signaling and possibly modulating miRNAs and highlights the pharmacotherapeutic potential of TNKS inhibition for prevention of IHF.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tanquirases / MicroRNAs / Insuficiência Cardíaca Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tanquirases / MicroRNAs / Insuficiência Cardíaca Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article