NDLI: Activation of endothelial β-catenin signaling induces heart failure

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Activation of endothelial β-catenin signaling induces heart failure

Content Provider	PubMed Central
Author	Nakagawa, Akito Naito, Atsuhiko T. Sumida, Tomokazu Nomura, Seitaro Masato, Shibamoto Higo, Tomoaki Okada, Katsuki Sakai, Taku Hashimoto, Akihito Kuramoto, Yuki Oka, Toru Lee, Jong-kook Harada, Mutsuo Ueda, Kazutaka Ichiro, Shiojima Limbourg, Florian P. Adams, Ralf H. Noda, Tetsuo Sakata, Yasushi Akazawa, Hiroshi Komuro, Issei
Copyright Year	2016
Abstract	Activation of β-catenin-dependent canonical Wnt signaling in endothelial cells plays a key role in angiogenesis during development and ischemic diseases, however, other roles of Wnt/β-catenin signaling in endothelial cells remain poorly understood. Here, we report that sustained activation of β-catenin signaling in endothelial cells causes cardiac dysfunction through suppressing neuregulin-ErbB pathway in the heart. Conditional gain-of-function mutation of β-catenin, which activates Wnt/β-catenin signaling in Bmx-positive arterial endothelial cells (Bmx/CA mice) led to progressive cardiac dysfunction and 100% mortality at 40 weeks after tamoxifen treatment. Electron microscopic analysis revealed dilatation of T-tubules and degeneration of mitochondria in cardiomyocytes of Bmx/CA mice, which are similar to the changes observed in mice with decreased neuregulin-ErbB signaling. Endothelial expression of Nrg1 and cardiac ErbB signaling were suppressed in Bmx/CA mice. The cardiac dysfunction of Bmx/CA mice was ameliorated by administration of recombinant neuregulin protein. These results collectively suggest that sustained activation of Wnt/β-catenin signaling in endothelial cells might be a cause of heart failure through suppressing neuregulin-ErbB signaling, and that the Wnt/β-catenin/NRG axis in cardiac endothelial cells might become a therapeutic target for heart failure.
Related Links	http://dx.doi.org/10.1038/srep25009
Starting Page	25009
File Format	PDF
ISSN	20452322
e-ISSN	20452322
Journal	Scientific Reports
Volume Number	6
Language	English
Publisher	Nature Publishing Group
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Science and technology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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