Discovery of a Small Molecule to Increase Cardiomyocytes and Protect the Heart After Ischemic Injury

被引：65

作者：

Hara, Hironori ^{[1
]}

Takeda, Norifumi ^{[1
]}

Kondo, Masaki ^{[2
]}

Kubota, Mio ^{[2
]}

Saito, Tatsuo ^{[2
]}

Maruyama, Junichi ^{[3
]}

Fujiwara, Takayuki ^{[1
]}

Maemura, Sonoko ^{[1
]}

Ito, Masamichi ^{[1
]}

Naito, Atsuhiko T. ^{[1
]}

Harada, Mutsuo ^{[1
]}

Toko, Haruhiro ^{[1
]}

Nomura, Seitaro ^{[1
,4
]}

Kumagai, Hidetoshi ^{[1
]}

Ikeda, Yuichi ^{[1
]}

Ueno, Hiroo ^{[5
]}

Takimoto, Eiki ^{[1
]}

Akazawa, Hiroshi ^{[1
]}

Morita, Hiroyuki ^{[1
]}

Aburatani, Hiroyuki ^{[4
]}

Hata, Yutaka ^{[3
]}

Uchiyama, Masanobu ^{[2
,6
,7
]}

Komuro, Issei ^{[1
]}

机构：

[1] Univ Tokyo Hosp, Dept Cardiovasc Med, Tokyo, Japan

[2] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan

[3] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Med Biochem, Tokyo, Japan

[4] Univ Tokyo, Res Ctr Adv Sci & Technol, Genome Sci Div, Tokyo, Japan

[5] Kansai Med Univ, Dept Stem Cell Pathol, Osaka, Japan

[6] RIKEN, Adv Elements Chem Res Team, RIKEN Ctr Sustainable Resource Sci, Wako, Saitama, Japan

[7] RIKEN, Elements Chem Lab, Wako, Saitama, Japan

来源：

JACC-BASIC TO TRANSLATIONAL SCIENCE | 2018年 / 3卷 / 05期

关键词：

antioxidation; Hippo pathway; myocardial infarction; regeneration; Wnt/beta-catenin signaling;

D O I：

10.1016/j.jacbts.2018.07.005

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Accumulating data suggest that new cardiomyocytes in adults are generated from existing cardiomyocytes throughout life. To enhance the endogenous cardiac regeneration, we performed chemical screenings to identify compounds that activate pro-proliferative YES-associated protein and transcriptional enhancer factor domain activities in cardiomyocytes. We synthesized a novel fluorine-containing TT-10 (C11H10FN3OS2) from the biologically hit compound. TT-10 promoted cardiomyocyte proliferation and simultaneously exerted antioxidant and antiapoptotic effects in vitro. TT-10 treatment in mice ameliorated myocardial infarction-induced cardiac dysfunction at least in part via enhancing clonal expansion of existing cardiomyocytes with nuclear YES-associated protein expression. Stimulating cardiomyocyte proliferation and/or protection with TT-10 might complement current therapies for myocardial infarction. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

引用

页码：639 / 653

页数：15

共 28 条

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YAP/TAZ Incorporation in the β-Catenin Destruction Complex Orchestrates the Wnt Response [J].