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Targeting GATA4 for cardiac repair.

Authors
  • Välimäki, Mika J1
  • Ruskoaho, Heikki J1
  • 1 Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. , (Finland)
Type
Published Article
Journal
IUBMB Life
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jan 01, 2020
Volume
72
Issue
1
Pages
68–79
Identifiers
DOI: 10.1002/iub.2150
PMID: 31419020
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Various strategies have been applied to replace the loss of cardiomyocytes in order to restore reduced cardiac function and prevent the progression of heart disease. Intensive research efforts in the field of cellular reprogramming and cell transplantation may eventually lead to efficient in vivo applications for the treatment of cardiac injuries, representing a novel treatment strategy for regenerative medicine. Modulation of cardiac transcription factor (TF) networks by chemical entities represents another viable option for therapeutic interventions. Comprehensive screening projects have revealed a number of molecular entities acting on molecular pathways highly critical for cellular lineage commitment and differentiation, including compounds targeting Wnt- and transforming growth factor beta (TGFβ)-signaling. Furthermore, previous studies have demonstrated that GATA4 and NKX2-5 are essential TFs in gene regulation of cardiac development and hypertrophy. For example, both of these TFs are required to fully activate mechanical stretch-responsive genes such as atrial natriuretic peptide and brain natriuretic peptide (BNP). We have previously reported that the compound 3i-1000 efficiently inhibited the synergy of the GATA4-NKX2-5 interaction. Cellular effects of 3i-1000 have been further characterized in a number of confirmatory in vitro bioassays, including rat cardiac myocytes and animal models of ischemic injury and angiotensin II-induced pressure overload, suggesting the potential for small molecule-induced cardioprotection. © 2019 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology.

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