Histamine deficiency exacerbates myocardial injury in acute myocardial infarction through impaired macrophage infiltration and increased cardiomyocyte apoptosis.
Histamine is a biogenic amine that is widely distributed and has multiple functions, but the role it plays in acute myocardial infarction (AMI) remains unclear. 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(+)Gr-1(+) immature myeloid cells (IMCs) that markedly increase in the early stages of AMI. Deficiency of histamine in HDC knockout mice (HDC(-/-)) reduced cardiac function and exacerbated the injury of infarcted heart. Furthermore, administering either an H1 receptor antagonist (pyrilamine) or an H2 receptor antagonist (cimetidine) demonstrated a protective effect of histamine against myocardial injury. The results of in vivo and in vitro assays showed that histamine deficiency promotes the apoptosis of cardiomyocytes and inhibits macrophage infiltration. In conclusion, CD11b(+)Gr-1(+) 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.
1] Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China [2] Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China [3].
Long
L
Deng
1] Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China [2] Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China [3].
Tao
T
Hong
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Jinyi
J
Lin
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Suling
S
Ding
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Zheyong
Z
Huang
1] Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China [2] Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Jinmiao
J
Chen
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Jianguo
J
Jia
1] Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China [2] Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Yunzeng
Y
Zou
Department of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Timothy C
TC
Wang
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Xiangdong
X
Yang
1] Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China [2] Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Junbo
J
Ge
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002927:Cimetidine / Q000494:pharmacology; D052279:Creatine Kinase, MB Form / Q000032:analysis; D004195:Disease Models, Animal; D006335:Heart Injuries / Q000209:etiology / Q000517:prevention & control; D006632:Histamine / Q000032:analysis / Q000494:pharmacology*; D006640:Histidine Decarboxylase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011738:Pyrilamine / Q000494:pharmacology
D002927:Cimetidine; D006632:Histamine; D052279:Creatine Kinase, MB Form; D006640:Histidine Decarboxylase; D011738:Pyrilamine