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(Circulation. 2000;102:806.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Increased Activity of Nuclear Factor-B Participates in Cardiovascular Remodeling Induced by Chronic Inhibition of Nitric Oxide Synthesis in Rats

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

From the Departments of Cardiovascular Medicine (S.K., K.E., C.K., M. Koyanagi, H.S., A.T.) and Pathology (K.S.), Graduate School of Medical Science, Kyushu University, Fukuoka; Division of Gene Therapy Sciences, Osaka University Medical School, Osaka (R.M., Y.K.); and Discovery Research Laboratory, Tanabe Sei-Yaku Co Ltd, Saitama (M. Katoh), Japan.

Correspondence to Kensuke Egashira, MD, PhD, Department of Cardiovascular Medicine, 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

Background—Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of N-nitro-L-arginine methyl ester (L-NAME) to rats induces early vascular inflammatory changes [monocyte infiltration into coronary vessels, nuclear factor-B (NF-B) 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-B 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-B in the pathogenesis of cardiovascular remodeling. We found here that in vivo transfection of cis element decoy oligodeoxynucleotides against NF-B to hearts prevented the L-NAME–induced early inflammation and subsequent coronary vascular medial thickening. In contrast, NF-B decoy oligodeoxynucleotide transfection did not decrease the development of fibrosis, the expression of transforming growth factor-ß₁ mRNA, or systolic pressure overload induced by L-NAME administration.

Conclusions—The NF-B 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.

Key Words: endothelium-derived factors • inflammation • proteins • cells • nitric oxide • nuclear factor-B

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