This Article Full Text Full Text (PDF) All Versions of this Article: 96/9/974    most recent 01.RES.0000166325.00383.edv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sasaguri, Y. Articles by Ohtsu, H. Search for Related Content PubMed PubMed Citation Articles by Sasaguri, Y. Articles by Ohtsu, H. Related Collections Pathophysiology Smooth muscle proliferation and differentiation Mechanism of atherosclerosis/growth factors

(Circulation Research. 2005;96:974.)
© 2005 American Heart Association, Inc.

Molecular Medicine

Role of Histamine Produced by Bone Marrow–Derived Vascular Cells in Pathogenesis of Atherosclerosis

Yasuyuki Sasaguri, Ke-Yong Wang, Akihide Tanimoto, Masato Tsutsui, Hikaru Ueno, Yoshitaka Murata, Yukari Kohno, Sohsuke Yamada, Hiroshi Ohtsu

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.

Correspondence to Yasuyuki Sasaguri, MD, PhD, Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental of Health, Kitakyushu 807-8555, Japan. 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) 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

This article has been cited by other articles:

				H. Wake, H. K. Takahashi, S. Mori, K. Liu, T. Yoshino, and M. Nishibori Histamine Inhibits Advanced Glycation End Products-Induced Adhesion Molecule Expression on Human Monocytes J. Pharmacol. Exp. Ther., September 1, 2009; 330(3): 826 - 833. [Abstract] [Full Text] [PDF]

				B. J. Bennett, S. S. Wang, X. Wang, X. Wu, and A. J. Lusis Genetic Regulation of Atherosclerotic Plaque Size and Morphology in the Innominate Artery of Hyperlipidemic Mice Arterioscler Thromb Vasc Biol, March 1, 2009; 29(3): 348 - 355. [Abstract] [Full Text] [PDF]

				F. Hao, M. Tan, X. Xu, and M.-Z. Cui Histamine Induces Egr-1 Expression in Human Aortic Endothelial Cells via the H1 Receptor-mediated Protein Kinase C{delta}-dependent ERK Activation Pathway J. Biol. Chem., October 3, 2008; 283(40): 26928 - 26936. [Abstract] [Full Text] [PDF]

				C. J. Pepine Provoked Coronary Spasm and Acute Coronary Syndromes J. Am. Coll. Cardiol., August 12, 2008; 52(7): 528 - 530. [Full Text] [PDF]

				S. Yamada, K.-Y. Wang, A. Tanimoto, J. Fan, S. Shimajiri, S. Kitajima, M. Morimoto, M. Tsutsui, T. Watanabe, K. Yasumoto, et al. Matrix Metalloproteinase 12 Accelerates the Initiation of Atherosclerosis and Stimulates the Progression of Fatty Streaks to Fibrous Plaques in Transgenic Rabbits Am. J. Pathol., May 1, 2008; 172(5): 1419 - 1429. [Abstract] [Full Text] [PDF]

				D. M. Hermann and C. M. Matter Tissue Plasminogen Activator Induced Reperfusion Injury After Stroke Revisited Circulation, July 24, 2007; 116(4): 363 - 365. [Full Text] [PDF]

				A. Tanimoto, K.-Y. Wang, Y. Murata, S. Kimura, M. Nomaguchi, S. Nakata, M. Tsutsui, and Y. Sasaguri Histamine Upregulates the Expression of Inducible Nitric Oxide Synthase in Human Intimal Smooth Muscle Cells via Histamine H1 Receptor and NF-{kappa}B Signaling Pathway Arterioscler Thromb Vasc Biol, July 1, 2007; 27(7): 1556 - 1561. [Abstract] [Full Text] [PDF]

				S. Koide, M. Okazaki, M. Tamura, K. Ozumi, H. Takatsu, F. Kamezaki, A. Tanimoto, H. Tasaki, Y. Sasaguri, Y. Nakashima, et al. PTEN reduces cuff-induced neointima formation and proinflammatory cytokines Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2824 - H2831. [Abstract] [Full Text] [PDF]

				K. Nakano, Y. Okada, K. Saito, R. Tanikawa, N. Sawamukai, Y. Sasaguri, T. Kohro, Y. Wada, T. Kodama, and Y. Tanaka Rheumatoid synovial endothelial cells produce macrophage colony-stimulating factor leading to osteoclastogenesis in rheumatoid arthritis Rheumatology, April 1, 2007; 46(4): 597 - 603. [Abstract] [Full Text] [PDF]