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Inhibition of β‐catenin/cyclic AMP Response Element‐binding Protein‐binding Protein Interaction by ICG‐001 Improves Contractile Function in Chronically Infarcted Rat Myocardium
Author(s) -
Hwang Hyosook,
Sasaki Tomoyo,
Kahn Michael,
Kloner Robert A.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1058.12
Subject(s) - wnt signaling pathway , ejection fraction , myocardial infarction , medicine , catenin , in vivo , cardiac function curve , cardiology , chemistry , endocrinology , beta catenin , ligation , signal transduction , heart failure , biology , biochemistry , microbiology and biotechnology
The adult heart has limited ability to repair after injury. Developing strategies that improve post‐infarct repair are needed. Wnt/β‐catenin signaling has been implicated in cardiac regeneration. We demonstrate that selective inhibition of the interaction between coactivator cyclic AMP response element‐binding protein‐binding protein, CBP and β‐catenin by a small molecule inhibitor ICG‐001 (ICG) benefits the infarcted myocardium. Rats undergoing coronary ligation received either ICG or pbs for 10 days. The left ventricular contractile function, infarct size, and remodeling were determined 4 weeks. ICG treatment significantly improved ejection fraction by 20%, compared to pbs. The increase in ejection fraction occurred without beneficial effects on infarct size, ventricular cavity volume, and infarcted wall thickness. To investigate the potential mechanism, proliferation and expressions of regenerative genes were studied at 7 days. BrdU positive cells, including myocytes, were observed in the epicardium of the infarcted wall in both groups. mRNA levels of c‐kit, Sca‐1, GATA‐4, and myosin were similar in both groups. Our data show that selective inhibition of β‐catenin/CBP interaction improves contractile function in the infarcted heart. We speculate that the effect of ICG is not in the proliferative phase; the exact mechanism whereby ICG‐001 has its positive effect remains to be determined.