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Targeting GATA4 for cardiac repair
Author(s) -
Välimäki Mika J.,
Ruskoaho Heikki J.
Publication year - 2020
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.2150
Subject(s) - reprogramming , gata4 , pressure overload , cardiac myocyte , wnt signaling pathway , transcription factor , myocyte , angiotensin ii , cardioprotection , regenerative medicine , atrial natriuretic peptide , microbiology and biotechnology , cardiac function curve , heart failure , medicine , biology , cancer research , signal transduction , cell , stem cell , receptor , ischemia , gene , cardiac hypertrophy , genetics , biochemistry
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.