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(Hypertension. 2000;35:86.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Role of Transforming Growth Factor-ß1 in Cardiovascular Inflammatory Changes Induced by Chronic Inhibition of Nitric Oxide Synthesis

Masamichi Koyanagi; Kensuke Egashira; Mayuko Kubo-Inoue; Makoto Usui; Shiro Kitamoto; Hideharu Tomita; Hiroaki Shimokawa; Akira Takeshita

From the Department of Cardiovascular Medicine, Cardiovascular Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Correspondence to Kensuke Egashira, MD, PhD, Department of Cardiovascular Medicine, Cardiovascular Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail egashira{at}cardiol.med.kyushu-u.ac.jp

Abstract—We previously reported that chronic inhibition of nitric oxide (NO) synthesis with N-nitro-L-arginine methyl ester (L-NAME) induces inflammatory changes (monocyte infiltration, myofibroblast formation, and monocyte chemoattractant protein-1 [MCP-1] and transforming growth factor-ß1 [TGF-ß1] expression) in the rat heart and vessel. There is debate regarding whether TGF-ß1 exhibits proinflammatory or anti-inflammatory activities. We used the rat model to investigate the role of TGF-ß in the pathogenesis of such inflammatory changes. We show here that infiltrating monocytes and myofibroblasts in the inflammatory lesions produced TGF-ß1 on the third day of L-NAME administration. Cotreatment with a monoclonal antibody against TGF-ß1, but not with control IgG, prevented the L-NAME–induced cardiac inflammation. The antibody also significantly inhibited the gene expression of MCP-1, P-selectin, and intercellular adhesion molecule-1. In summary, the antibody against TGF-ß1 prevented inflammatory changes in rat heart and vessel induced by chronic inhibition of NO synthesis, suggesting that increased production of TGF-ß1 is involved in the inflammatory changes in this model.

Key Words: endothelium-derived factor • growth substances • inflammation • adhesion molecule • angiotensin II • fibrosis

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