Published online before print April 14, 2005, doi: 10.1161/01.RES.0000166325.00383.ed
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Submitted on December 16, 2004
Revised on March 22, 2005
Accepted on April 6, 2005
Role of Histamine Produced by Bone Marrow-Derived Vascular Cells in Pathogenesis of Atherosclerosis
Yasayuki Sasaguri *;
From the Department of Pathology and Cell Biology (Y.S., K.-Y.W., Y.K., S.Y.), School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu; Department of Pathology (A.T.), Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Minato-ku, Tokyo; Department of Pharmacology (M.T.), School of Medicine, University of Occupational and Environmental Health; Department of Biochemistry and Molecular Pathophysiology (H.U.), School of Medicine, University of Occupational and Environmental Health; Department of Kyurin Omtest Laboratory (Y.M.), Kyurin Pacell Corporation, Takanosu, Yahatanishi-ku, Kitakyushu; and the Department of Quantum Science and Energy Engineering (H.O.), School of Engineering, Tohoku University, Aoba-ku, Sendai, Japan.
* To whom correspondence should be addressed. E-mail: yasu-s{at}med.uoeh-u.ac.jp.
To clarify the role of histamine-producing cells and its origin in atherosclerosis, we investigated histidine decarboxylase (HDC; histamine-producing enzyme) expression in murine arteries with vascular injuries after the animal had received transplanted bone marrow (BM) from green fluorescent protein (GFP)-transgenic mice. The neointima in the ligated carotid arteries contained BM-derived HDC+ cells that expressed macrophage (Mac-3) and/or smooth muscle cell antigen (
-SMA). In contrast, the HDC+ BM-derived cells, which were positive for Mac-3, were mainly located in the adventitia in the cuff replacement model. In apolipoprotein E-knockout mice on a high cholesterol diet, BM-derived cells expressing Mac-3 in the atheromatous plaques were also positive for HDC. In comparison with wild-type mice, HDC-/- mice showed reduced neointimal thickening and a decreased intima-to-media ratio after ligation and cuff replacement. These results indicate that histamine produced from BM-derived progenitor cells, which could transdifferentiate into SMC- or macrophage-like cells, are important for the formation of neointima and atheromatous plaques.
Key words: histamine • histidine decarboxylase • progenitor cells • bone marrow • vascular injury
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