Histamine receptors expressed in circulating progenitor cells have reciprocal actions in ligation-induced arteriosclerosis

Authors

  • Sohsuke Yamada,

    Corresponding author
    • Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
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  • Ke-Yong Wang,

    1. Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
    2. Department of Bio-information Research Center, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
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  • Akihide Tanimoto,

    1. Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
    2. Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima
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  • Xin Guo,

    1. Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
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  • Atsunori Nabeshima,

    1. Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
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  • Takeshi Watanabe,

    1. Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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  • Yasuyuki Sasaguri

    1. Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu
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  • Conflict of interest and funding disclosures: None declared.

Correspondence: Sohsuke Yamada, MD, PhD, Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. Email: sousuke@med.uoeh-u.ac.jp

Abstract

Histamine is synthesized as a low-molecular-weight amine from L-histidine by histidine decarboxylase (HDC). Recently, we demonstrated that carotid artery-ligated HDC gene-deficient mice (HDC–/–) showed less neointimal formation than wild-type (WT) mice, indicating that histamine participates in the process of arteriosclerosis. However, little is known about the roles of histamine-specific receptors (HHRs) in arteriosclerosis. To define the roles of HHRs in arteriosclerosis, we investigated intimal remodeling in ligated carotid arteries of HHR-deficient mice (H1R–/– or H2R–/–). Quantitative analysis showed that H1R–/– mice had significantly less arteriosclerogenesis, whereas H2R–/– mice had more, as compared with WT mice. Bone marrow transplantation from H1R–/– or H2R–/– to WT mice confirmed the above observation. Furthermore, the increased expression of monocyte chemoattractant protein (MCP-1), platelet-derived growth factor (PDGF), adhesion molecules and liver X receptor (LXR)-related inflammatory signaling factors, including Toll-like receptor (TLR3), interleukin-1 receptor (IL-1R) and tumor necrosis factor receptor (TNF-R), was consistent with the arteriosclerotic phenotype of H2R–/– mice. Peripheral progenitor cells in H2R–/– mice accelerate ligation-induced arteriosclerosis through their regulation of MCP-1, PDGF, adhesion molecules and LXR-related inflammatory signaling factors. In contrast, peripheral progenitor cells act to suppress arteriosclerosis in H1R–/– mice, indicating that HHRs reciprocally regulate inflammation in the ligation-induced arteriosclerosis.

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