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In this study, we investigated the origin and contribution of endogenous histamine to AMI. Histidine decarboxylase (HDC) is the unique enzyme responsible for histamine generation. Using HDC-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the HDC promoter, we identified HDC expression primarily in CD11b<jats:sup>+<\/jats:sup>Gr-1<jats:sup>+<\/jats:sup>immature myeloid cells (IMCs) that markedly increase in the early stages of AMI. Deficiency of histamine in HDC knockout mice (HDC<jats:sup>\u2212\/\u2212<\/jats:sup>) reduced cardiac function and exacerbated the injury of infarcted heart. Furthermore, administering either an H<jats:sub>1<\/jats:sub>receptor antagonist (pyrilamine) or an H<jats:sub>2<\/jats:sub>receptor antagonist (cimetidine) demonstrated a protective effect of histamine against myocardial injury. The results of<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>assays showed that histamine deficiency promotes the apoptosis of cardiomyocytes and inhibits macrophage infiltration. In conclusion, CD11b<jats:sup>+<\/jats:sup>Gr-1<jats:sup>+<\/jats:sup>IMCs are the predominant HDC-expressing sites in AMI and histamine plays a protective role in the process of AMI through inhibition of cardiomyocyte apoptosis and facilitation of macrophage infiltration.<\/jats:p>","DOI":"10.1038\/srep13131","type":"journal-article","created":{"date-parts":[[2015,8,17]],"date-time":"2015-08-17T10:47:34Z","timestamp":1439808454000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Histamine deficiency exacerbates myocardial injury in acute myocardial infarction through impaired macrophage infiltration and increased cardiomyocyte apoptosis"],"prefix":"10.1038","volume":"5","author":[{"given":"Long","family":"Deng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suling","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheyong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinmiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianguo","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunzeng","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy C.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangdong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junbo","family":"Ge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,8,17]]},"reference":[{"key":"BFsrep13131_CR1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.cardiores.2005.01.011","volume":"66","author":"G Ertl","year":"2005","unstructured":"Ertl, G. & Frantz, S. 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