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Histidine decarboxylase (HDC) is the main enzyme involved in histamine production. Here, we clarified the roles of HDC-expressing cells and histamine in heart failure post-MI using HDC-EGFP transgenic mice and HDC-knockout (HDC<jats:sup>\u2212\/\u2212<\/jats:sup>) mice. HDC<jats:sup>+<\/jats:sup>CD11b<jats:sup>+<\/jats:sup> myeloid cell numbers markedly increased in the injured hearts, and histamine levels were up-regulated in the circulation post-MI. HDC<jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited more adverse cardiac remodeling, poorer left ventricular function and higher mortality by increasing cardiac fibrogenesis post-MI. <jats:italic>In vitro<\/jats:italic> assays further confirmed that histamine inhibited heart fibroblast proliferation. Furthermore, histamine enhanced the signal transducer and activator of transcription (STAT)-6 phosphorylation level in murine heart fibroblasts, and the inhibitive effects of histamine on fibroblast proliferation could be blocked by JAK3\/STAT6 signaling selective antagonist. STAT6-knockout (STAT6<jats:sup>\u2212\/\u2212<\/jats:sup>) mice had a phenotype similar to that of HDC<jats:sup>\u2212\/\u2212<\/jats:sup> mice post-MI; however, in contrast to HDC<jats:sup>\u2212\/\u2212<\/jats:sup> mice, the beneficial effects of exogenous histamine injections were abrogated in STAT6<jats:sup>\u2212\/\u2212<\/jats:sup> mice. These data suggest that histamine exerts protective effects by modulating cardiac fibrosis and remodeling post-MI, in part through the STAT6-dependent signaling pathway.<\/jats:p>","DOI":"10.1038\/srep44007","type":"journal-article","created":{"date-parts":[[2017,3,8]],"date-time":"2017-03-08T10:07:48Z","timestamp":1488967668000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Aggravated myocardial infarction-induced cardiac remodeling and heart failure in histamine-deficient mice"],"prefix":"10.1038","volume":"7","author":[{"given":"Jinmiao","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suling","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieradilijiang","family":"Abudupataer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghong","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzeng","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy C.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,8]]},"reference":[{"key":"BFsrep44007_CR1","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/s0140-6736(11)61038-6","volume":"378","author":"H Krum","year":"2011","unstructured":"Krum, H. & Teerlink, J. 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