title: Histamine receptors expressed in circulating progenitor cells have reciprocal actions in ligation-induced arteriosclerosis.
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.
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu.
authors.forename: Sohsuke
authors.initials: S
authors.lastname: Yamada
authors.forename: Ke-Yong
authors.initials: KY
authors.lastname: Wang
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nabeshima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D006632:Histamine / Q000378:metabolism; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011968:Receptors, Histamine / Q000235:genetics / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D010982:Platelet-Derived Growth Factor; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine; D006640:Histidine Decarboxylase
keywords: MCP‐1; Toll‐like receptors; arteriosclerosis; histamine; histamine receptors