Role of Transforming Growth Factor-β1 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

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58 Citations (Scopus)

Abstract

We previously reported that chronic inhibition of nitric oxide (NO) synthesis with Nω-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-β1 [TGF-β1] expression) in the rat heart and vessel. There is debate regarding whether TGF-β1 exhibits proinflammatory or anti-inflammatory activities. We used the rat model to investigate the role of TGF-β in the pathogenesis of such inflammatory changes. We show here that infiltrating monocytes and myofibroblasts in the inflammatory lesions produced TGF-β1 on the third day of L-NAME administration. Cotreatment with a monoclonal antibody against TGF-β1, 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-β1 prevented inflammatory changes in rat heart and vessel induced by chronic inhibition of NO synthesis, suggesting that increased production of TGF-β1 is involved in the inflammatory changes in this model.

Original languageEnglish
Number of pages1
JournalHypertension
Volume35
Issue number1
DOIs
Publication statusPublished - Jan 2000

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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    Koyanagi, M., Egashira, K., Kubo-Inoue, M., Usui, M., Kitamoto, S., Tomita, H., Shimokawa, H., & Takeshita, A. (2000). Role of Transforming Growth Factor-β1 in Cardiovascular Inflammatory Changes Induced by Chronic Inhibition of Nitric Oxide Synthesis. Hypertension, 35(1). https://doi.org/10.1161/01.HYP.35.1.86