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Here, we report that sustained activation of \u03b2-catenin signaling in endothelial cells causes cardiac dysfunction through suppressing neuregulin-ErbB pathway in the heart. Conditional gain-of-function mutation of \u03b2-catenin, which activates Wnt\/\u03b2-catenin signaling in <jats:italic>Bmx<\/jats:italic>-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 <jats:italic>Nrg1<\/jats:italic> 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\/\u03b2-catenin signaling in endothelial cells might be a cause of heart failure through suppressing neuregulin-ErbB signaling and that the Wnt\/\u03b2-catenin\/NRG axis in cardiac endothelial cells might become a therapeutic target for heart failure.<\/jats:p>","DOI":"10.1038\/srep25009","type":"journal-article","created":{"date-parts":[[2016,5,5]],"date-time":"2016-05-05T09:04:23Z","timestamp":1462439063000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Activation of endothelial \u03b2-catenin signaling induces heart failure"],"prefix":"10.1038","volume":"6","author":[{"given":"Akito","family":"Nakagawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuhiko T.","family":"Naito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomokazu","family":"Sumida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seitaro","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Shibamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoaki","family":"Higo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuki","family":"Okada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihito","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Kuramoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Oka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Kook","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mutsuo","family":"Harada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazutaka","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiro","family":"Shiojima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian P.","family":"Limbourg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf H.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuo","family":"Noda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Sakata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Akazawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Issei","family":"Komuro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,5,5]]},"reference":[{"key":"BFsrep25009_CR1","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1161\/circresaha.114.300507","volume":"114","author":"T Oka","year":"2014","unstructured":"Oka, T., Akazawa, H., Naito, A. 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