The small molecule Wnt signaling modulator ICG-001 improves contractile function in chronically infarcted rat myocardium.
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.
Department of Biochemistry and Molecular Biology, Keck School of Medicine of University of Southern California, Los Angeles, California, United States of America.
Tomoyo
T
Sasaki
Hyosook
H
Hwang
Cu
C
Nguyen
Robert A
RA
Kloner
Michael
M
Kahn
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D032386:Myoblasts, Cardiac / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication; D010496:Pericardium / Q000166:cytology / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D011744:Pyrimidinones / Q000494:pharmacology*; D051381:Rats; D012038:Regeneration; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
D019086:Bridged Bicyclo Compounds, Heterocyclic; D055436:Growth Differentiation Factor 15; C492448:ICG 001; D011744:Pyrimidinones; D051176:beta Catenin; D019009:Proto-Oncogene Proteins c-kit