title: Aggravated myocardial infarction-induced cardiac remodeling and heart failure in histamine-deficient mice.
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.
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.|Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Jinmiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.|Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hong
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Suling
authors.initials: S
authors.lastname: Ding
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.|Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Long
authors.initials: L
authors.lastname: Deng
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.|Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Mieradilijiang
authors.initials: M
authors.lastname: Abudupataer
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Clinical Medicine, TongRen Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, 200000, China.
authors.forename: Minghong
authors.initials: M
authors.lastname: Tong
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Jia
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gong
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006632:Histamine / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000172:deficiency / Q000235:genetics; D006801:Humans; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000662:veterinary; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D010766:Phosphorylation; D011968:Receptors, Histamine / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D016207:Cytokines; D011968:Receptors, Histamine; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D006632:Histamine; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3; D006640:Histidine Decarboxylase