This Article Full Text Full Text (PDF) 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 Matsumura, T. Articles by Yasue, H. Search for Related Content PubMed PubMed Citation Articles by Matsumura, T. Articles by Yasue, H. Related Collections Animal models of human disease Lipid and lipoprotein metabolism

(Circulation. 1999;99:919-924.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Suppression of Atherosclerotic Development in Watanabe Heritable Hyperlipidemic Rabbits Treated With an Oral Antiallergic Drug, Tranilast

Toshiyuki Matsumura, MD; Kiyotaka Kugiyama, MD; Seigo Sugiyama, MD; Yasutaka Ota, MD; Hideki Doi, MD; Nobuhiko Ogata, MD; Hideki Oka, MD; Hirofumi Yasue, MD

From the Division of Cardiology, Kumamoto University School of Medicine, Japan.

Correspondence to Kiyotaka Kugiyama, MD, Division of Cardiology, Kumamoto University School of Medicine, Kumamoto City, Japan 860. E-mail kiyo{at}gpo.kumamoto-u.ac.jp

Background—Inflammatory and immunological responses of vascular cells have been shown to play a significant role in the progression of atheromatous formation. Tranilast [N-(3,4-dimethoxycinnamoyl) anthranillic acid] inhibits release of cytokines and chemical mediators from various cells, including macrophages, leading to suppression of inflammatory and immunological responses. This study tested whether tranilast may suppress atheromatous formation in Watanabe heritable hyperlipidemic (WHHL) rabbits.

Methods and Results—WHHL rabbits (2 months old) were given either 300 mg · kg^-1 · d^-1 of tranilast (Tranilast, n=12) or vehicle (Control, n=13) PO for 6 months. Tranilast treatment was found to suppress the aortic area covered with plaque. Immunohistochemical analysis showed that there was no difference in the percentage of the RAM11-positive macrophage area and the frequency of CD5-positive cells (T cells) in intimal plaques between Tranilast and Control. Major histocompatibility complex (MHC) class II expression in macrophages and interleukin-2 (IL-2) receptor expression in T cells, as markers of the immunological activation in these cells, was suppressed in atheromatous plaque by tranilast treatment. Flow cytometry analysis of isolated human and rabbit peripheral blood mononuclear cells showed that an increase in expression both of MHC class II antigen on monocytes by incubation with interferon- and of IL-2 receptor on T cells by IL-2 was suppressed by the combined incubation with tranilast.

Conclusions—The results indicate that tranilast suppresses atherosclerotic development partly through direct inhibition of immunological activation of monocytes/macrophages and T cells in the atheromatous plaque.

Key Words: atherosclerosis • cells • lymphocytes • immune system

This article has been cited by other articles:

				E. A. Capper, A. K. Roshak, B. J. Bolognese, P. L. Podolin, T. Smith, D. L. Dewitt, K. M. Anderson, and L. A. Marshall Modulation of Human Monocyte Activities by Tranilast, SB 252218, a Compound Demonstrating Efficacy in Restenosis J. Pharmacol. Exp. Ther., December 1, 2000; 295(3): 1061 - 1069. [Abstract] [Full Text]