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Sci Rep. 2017 Mar 8;7:44007. doi: 10.1038/srep44007.

Aggravated myocardial infarction-induced cardiac remodeling and heart failure in histamine-deficient mice.

Author information

1
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
2
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
3
Department of Clinical Medicine, TongRen Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, 200000, China.
4
Department of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.

Abstract

Histamine has pleiotropic pathophysiological effects, but its role in myocardial infarction (MI)-induced cardiac remodeling remains unclear. 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-/-) mice. HDC+CD11b+ myeloid cell numbers markedly increased in the injured hearts, and histamine levels were up-regulated in the circulation post-MI. HDC-/- mice exhibited more adverse cardiac remodeling, poorer left ventricular function and higher mortality by increasing cardiac fibrogenesis post-MI. In vitro 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-/-) mice had a phenotype similar to that of HDC-/- mice post-MI; however, in contrast to HDC-/- mice, the beneficial effects of exogenous histamine injections were abrogated in STAT6-/- 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.

PMID:
28272448
PMCID:
PMC5341031
DOI:
10.1038/srep44007
[Indexed for MEDLINE]
Free PMC Article

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