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Activation of endothelial β-catenin signaling induces heart failure
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-cate...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857119/ https://www.ncbi.nlm.nih.gov/pubmed/27146149 http://dx.doi.org/10.1038/srep25009 |
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author | Nakagawa, Akito Naito, Atsuhiko T. Sumida, Tomokazu Nomura, Seitaro Shibamoto, Masato Higo, Tomoaki Okada, Katsuki Sakai, Taku Hashimoto, Akihito Kuramoto, Yuki Oka, Toru Lee, Jong-Kook Harada, Mutsuo Ueda, Kazutaka Shiojima, Ichiro Limbourg, Florian P. Adams, Ralf H. Noda, Tetsuo Sakata, Yasushi Akazawa, Hiroshi Komuro, Issei |
author_facet | Nakagawa, Akito Naito, Atsuhiko T. Sumida, Tomokazu Nomura, Seitaro Shibamoto, Masato Higo, Tomoaki Okada, Katsuki Sakai, Taku Hashimoto, Akihito Kuramoto, Yuki Oka, Toru Lee, Jong-Kook Harada, Mutsuo Ueda, Kazutaka Shiojima, Ichiro Limbourg, Florian P. Adams, Ralf H. Noda, Tetsuo Sakata, Yasushi Akazawa, Hiroshi Komuro, Issei |
author_sort | Nakagawa, Akito |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4857119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48571192016-05-19 Activation of endothelial β-catenin signaling induces heart failure Nakagawa, Akito Naito, Atsuhiko T. Sumida, Tomokazu Nomura, Seitaro Shibamoto, Masato Higo, Tomoaki Okada, Katsuki Sakai, Taku Hashimoto, Akihito Kuramoto, Yuki Oka, Toru Lee, Jong-Kook Harada, Mutsuo Ueda, Kazutaka Shiojima, Ichiro Limbourg, Florian P. Adams, Ralf H. Noda, Tetsuo Sakata, Yasushi Akazawa, Hiroshi Komuro, Issei Sci Rep Article 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. Nature Publishing Group 2016-05-05 /pmc/articles/PMC4857119/ /pubmed/27146149 http://dx.doi.org/10.1038/srep25009 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Nakagawa, Akito Naito, Atsuhiko T. Sumida, Tomokazu Nomura, Seitaro Shibamoto, Masato Higo, Tomoaki Okada, Katsuki Sakai, Taku Hashimoto, Akihito Kuramoto, Yuki Oka, Toru Lee, Jong-Kook Harada, Mutsuo Ueda, Kazutaka Shiojima, Ichiro Limbourg, Florian P. Adams, Ralf H. Noda, Tetsuo Sakata, Yasushi Akazawa, Hiroshi Komuro, Issei Activation of endothelial β-catenin signaling induces heart failure |
title | Activation of endothelial β-catenin signaling induces heart failure |
title_full | Activation of endothelial β-catenin signaling induces heart failure |
title_fullStr | Activation of endothelial β-catenin signaling induces heart failure |
title_full_unstemmed | Activation of endothelial β-catenin signaling induces heart failure |
title_short | Activation of endothelial β-catenin signaling induces heart failure |
title_sort | activation of endothelial β-catenin signaling induces heart failure |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857119/ https://www.ncbi.nlm.nih.gov/pubmed/27146149 http://dx.doi.org/10.1038/srep25009 |
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