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PMID: 24069374 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

The small molecule Wnt signaling modulator ICG-001 improves contractile function in chronically infarcted rat myocardium.

PloS one ·Vol. 8 ·No. 9 ·2013-00-00 ·Pages e75010

Sasaki T, Hwang H, Nguyen C, Kloner RA, Kahn M

Abstract

The adult mammalian heart has limited capability for self-repair after myocardial infarction. Therefore, therapeutic strategies that improve post-infarct cardiac function are critically needed. The small molecule ICG-001 modulates Wnt signaling and increased the expression of genes beneficial for cardiac regeneration in epicardial cells. Lineage tracing experiments, demonstrated the importance of β-catenin/p300 mediated transcription for epicardial progenitor contribution to the myocardium. Female rats given ICG-001 for 10 days post-occlusion significantly improved ejection fraction by 8.4%, compared to controls (P<0.05). Taken together, Wnt modulation via β-catenin/CBP inhibition offers a promising therapeutic strategy towards restoration of myocardial tissues and an enhancement of cardiac functions following infarction.

MeSH Terms
Animals Bridged Bicyclo Compounds, Heterocyclic/pharmacology Disease Models, Animal Epithelial-Mesenchymal Transition/drug effects Female Gene Expression Regulation/drug effects Growth Differentiation Factor 15/genetics,metabolism Muscle Contraction/drug effects Myoblasts, Cardiac/drug effects,metabolism Myocardial Infarction/genetics,metabolism,physiopathology Myocardium/metabolism,pathology Paracrine Communication Pericardium/cytology,metabolism Proto-Oncogene Proteins c-kit/genetics,metabolism Pyrimidinones/pharmacology Rats Regeneration Wnt Signaling Pathway/drug effects beta Catenin/metabolism
Chemicals
Bridged Bicyclo Compounds, Heterocyclic Growth Differentiation Factor 15 ICG 001 Pyrimidinones beta Catenin Proto-Oncogene Proteins c-kit
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sasaki Tomoyo
Department of Biochemistry and Molecular Biology, Keck School of Medicine of University of Southern California, Los Angeles, California, United States of America.
Hwang Hyosook
Nguyen Cu
Kloner Robert A
Kahn Michael
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0075010
Published
2013-00-00
Epub
2013-00-12
Pages
e75010
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3771968
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0075010 PMC Full Text View journal details
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