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Histamine receptors expressed in circulating progenitor cells have reciprocal actions in ligation‐induced arteriosclerosis
Author(s) -
Yamada Sohsuke,
Wang KeYong,
Tanimoto Akihide,
Guo Xin,
Nabeshima Atsunori,
Watanabe Takeshi,
Sasaguri Yasuyuki
Publication year - 2013
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/pin.12091
Subject(s) - arteriosclerosis , endocrinology , histamine , medicine , receptor , inflammation , progenitor cell , chemistry , biology , microbiology and biotechnology , stem cell
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 T oll‐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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