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As several \u03b2-arrestin-biased agonists have been reported to be cardioprotective, we examined the role of the chemokine receptor CXCR7 as a \u03b2-arrestin-biased receptor in the heart. Among 510 7TMR genes examined, <jats:italic>Cxcr7<\/jats:italic> was the most abundantly expressed in the murine heart. Single-cell RNA-sequencing analysis revealed that <jats:italic>Cxcr7<\/jats:italic> was abundantly expressed in cardiomyocytes and fibroblasts. Cardiomyocyte-specific <jats:italic>Cxcr7<\/jats:italic> null mice showed more prominent cardiac dilatation and dysfunction than control mice 4\u00a0weeks after myocardial infarction. In contrast, there was no difference in cardiac phenotypes between fibroblast-specific <jats:italic>Cxcr7<\/jats:italic>-knockout mice and control mice even after myocardial infarction. TC14012, a specific agonist of CXCR7, significantly recruited \u03b2-arrestin to CXCR7 in CXCR7-expressing cells and activated extracellular signal-regulated kinase (ERK) in neonatal rat cardiomyocytes. <jats:italic>Cxcr7<\/jats:italic> expression was significantly increased and ERK was activated in the border zone of the heart in control, but not <jats:italic>Cxcr7<\/jats:italic> null mice. These results indicate that the abundantly expressed CXCR7 in cardiomyocytes may play a protective role in the heart as a \u03b2-arrestin-biased receptor and that CXCR7 may be a novel therapeutic target for myocardial infarction.<\/jats:p>","DOI":"10.1038\/s41598-021-83022-5","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T21:23:32Z","timestamp":1612905812000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["CXCR7 ameliorates myocardial infarction as a \u03b2-arrestin-biased receptor"],"prefix":"10.1038","volume":"11","author":[{"given":"Masato","family":"Ishizuka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutsuo","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seitaro","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Bujo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Yanagisawa-Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Satoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Kumagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Motozawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuyuki","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norifumi","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiko","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinya","family":"Otsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiro","family":"Toko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issei","family":"Komuro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"key":"83022_CR1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s12551-014-0154-2","volume":"7","author":"SR Foster","year":"2015","unstructured":"Foster, S. 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