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

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75 Citations (Scopus)


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
Issue number7
Publication statusPublished - Jan 1 2000


All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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