Sci Rep. 2015 Aug 17;5:13131. doi: 10.1038/srep13131.

Histamine deficiency exacerbates myocardial injury in acute myocardial infarction through impaired macrophage infiltration and increased cardiomyocyte apoptosis.

Deng L1, Hong T1, Lin J2, Ding S2, Huang Z2, Chen J3, Jia J2, Zou Y4, Wang TC5, Yang X2, Ge J4.

• 11] 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].
• 2Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
• 31] Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China [2] Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
• 41] Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China [2] Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
• 5Department of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.

Abstract

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.

PMID:  26278136