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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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 1 2000

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Transforming Growth Factors
Nitric Oxide
NG-Nitroarginine Methyl Ester
Myofibroblasts
Chemokine CCL2
Monocytes
P-Selectin
Antibodies
Intercellular Adhesion Molecule-1
Anti-Inflammatory Agents
Immunoglobulin G
Monoclonal Antibodies
Inflammation
Gene Expression

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Role of Transforming Growth Factor-β1 in Cardiovascular Inflammatory Changes Induced by Chronic Inhibition of Nitric Oxide Synthesis. / Koyanagi, Masamichi; Egashira, Kensuke; Kubo-Inoue, Mayuko; Usui, Makoto; Kitamoto, Shiro; Tomita, Hideharu; Shimokawa, Hiroaki; Takeshita, Akira.

In: Hypertension, Vol. 35, No. 1, 01.01.2000.

Research output: Contribution to journalArticle

Koyanagi, Masamichi ; Egashira, Kensuke ; Kubo-Inoue, Mayuko ; Usui, Makoto ; Kitamoto, Shiro ; Tomita, Hideharu ; Shimokawa, Hiroaki ; Takeshita, Akira. / Role of Transforming Growth Factor-β1 in Cardiovascular Inflammatory Changes Induced by Chronic Inhibition of Nitric Oxide Synthesis. In: Hypertension. 2000 ; Vol. 35, No. 1.
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