Targeting GATA4 for cardiac repair

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http://hdl.handle.net/10138/311539

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Välimäki , M J & Ruskoaho , H J 2020 , ' Targeting GATA4 for cardiac repair ' , IUBMB Life , vol. 72 , no. 1 , pp. 68-79 . https://doi.org/10.1002/iub.2150

Title: Targeting GATA4 for cardiac repair
Author: Välimäki, Mika J.; Ruskoaho, Heikki J.
Contributor: University of Helsinki, Division of Pharmacology and Pharmacotherapy
University of Helsinki, Division of Pharmacology and Pharmacotherapy
Date: 2020-01
Language: eng
Number of pages: 12
Belongs to series: IUBMB Life
ISSN: 1521-6543
URI: http://hdl.handle.net/10138/311539
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 (TGF beta)-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.
Subject: medicinal chemistry
protein function
transcription factors
transcriptional regulation
TRANSCRIPTION FACTOR GATA-4
STRESS-INDUCED ACTIVATION
EMBRYONIC STEM-CELLS
GENE-EXPRESSION
DNA-BINDING
MYOCARDIAL-INFARCTION
HEART REGENERATION
HYPERTROPHY
SURVIVAL
REVEALS
116 Chemical sciences
1182 Biochemistry, cell and molecular biology
317 Pharmacy
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