Increased activity of nuclear factor-κB participates in cardiovascular remodeling induced by chronic inhibition of nitric oxide synthesis in rats

Shiro Kitamoto, Kensuke Egashira, Chu Kataoka, Masamichi Koyanagi, Makoto Katoh, Hiroaki Shimokawa, Ryuichi Morishita, Yasufumi Kaneda, Katsuo Sueishi, Akira Takeshita

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Background - Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of N(ω)-nitro-L-arginine methyl ester (L-NAME) to rats induces early vascular inflammatory changes [monocyte infiltration into coronary vessels, nuclear factor-κB (NF-κB) activation, and monocyte chemoattractant protein-1 expression] as well as subsequent arteriosclerosis (medial thickening and perivascular fibrosis) and cardiac fibrosis. However, no direct evidence for the importance of NF-κB in this process is known. Methods and Results - We examined the effect of a cis element decoy strategy to address the functional importance of NF-κB in the pathogenesis of cardiovascular remodeling. We found here that in vivo transfection of cis element decoy oligodeoxynucleotides against NF-κB to hearts prevented the L-NAME - induced early inflammation and subsequent coronary vascular medial thickening. In contrast, NF-κB decoy oligodeoxynucleotide transfection did not decrease the development of fibrosis, the expression of transforming growth factor-β1 mRNA, or systolic pressure overload induced by L-NAME administration. Conclusions - The NF-κB system participates importantly in the development of early vascular inflammation and subsequent medial thickening but not in fibrogenesis in this model. The present study may provide a new aspect of how endothelium-derived NO contributes to anti-inflammatory and/or antiarteriosclerotic properties of the vascular endothelium in vivo.

Original languageEnglish
Pages (from-to)806-812
Number of pages7
JournalCirculation
Volume102
Issue number7
DOIs
Publication statusPublished - Jan 1 2000

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NG-Nitroarginine Methyl Ester
Blood Vessels
Nitric Oxide
Fibrosis
Oligodeoxyribonucleotides
Transfection
Inflammation
Arteriosclerosis
Chemokine CCL2
Vascular Endothelium
Transforming Growth Factors
Monocytes
Coronary Vessels
Anti-Inflammatory Agents
Blood Pressure
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Increased activity of nuclear factor-κB participates in cardiovascular remodeling induced by chronic inhibition of nitric oxide synthesis in rats. / Kitamoto, Shiro; Egashira, Kensuke; Kataoka, Chu; Koyanagi, Masamichi; Katoh, Makoto; Shimokawa, Hiroaki; Morishita, Ryuichi; Kaneda, Yasufumi; Sueishi, Katsuo; Takeshita, Akira.

In: Circulation, Vol. 102, No. 7, 01.01.2000, p. 806-812.

Research output: Contribution to journalArticle

Kitamoto, S, Egashira, K, Kataoka, C, Koyanagi, M, Katoh, M, Shimokawa, H, Morishita, R, Kaneda, Y, Sueishi, K & Takeshita, A 2000, 'Increased activity of nuclear factor-κB participates in cardiovascular remodeling induced by chronic inhibition of nitric oxide synthesis in rats', Circulation, vol. 102, no. 7, pp. 806-812. https://doi.org/10.1161/01.CIR.102.7.806
Kitamoto, Shiro ; Egashira, Kensuke ; Kataoka, Chu ; Koyanagi, Masamichi ; Katoh, Makoto ; Shimokawa, Hiroaki ; Morishita, Ryuichi ; Kaneda, Yasufumi ; Sueishi, Katsuo ; Takeshita, Akira. / Increased activity of nuclear factor-κB participates in cardiovascular remodeling induced by chronic inhibition of nitric oxide synthesis in rats. In: Circulation. 2000 ; Vol. 102, No. 7. pp. 806-812.
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AU - Katoh, Makoto

AU - Shimokawa, Hiroaki

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