Importance of endothelial NF-κB signalling in vascular remodelling and aortic aneurysm formation

Tokuo Saito, Yutaka Hasegawa, Yasushi Ishigaki, Tetsuya Yamada, Junhong Gao, Junta Imai, Kenji Uno, Keizo Kaneko, Takehide Ogihara, Tatsuo Shimosawa, Tomoichiro Asano, Toshiro Fujita, Yoshitomo Oka, Hideki Katagiri

研究成果: Article査読

69 被引用数 (Scopus)

抄録

Aims Vascular remodelling and aortic aneurysm formation are induced mainly by inflammatory responses in the adventitia and media. However, relatively little is known about the mechanistic significance of endothelium in the pathogenesis of these vascular disorders. The transcription factor nuclear factor-kappa B (NF-κB) regulates the expressions of numerous genes, including those related to pro-inflammatory responses. Therefore, to investigate the roles of endothelial pro-inflammatory responses, we examined the impact of blocking endothelial NF-κB signalling on intimal hyperplasia and aneurysm formation.Methods and resultsTo block endothelial NF-κB signalling, we used transgenic mice expressing dominant-negative IκBα selectively in endothelial cells (E-DNIκB mice). E-DNIκB mice were protected from the development of cuff injury-induced neointimal formation, in association with suppressed arterial expressions of cellular adhesion molecules, a macrophage marker, and inflammatory factors. In addition, the blockade of endothelial NF-κB signalling prevented abdominal aortic aneurysm formation in an experimental model, hypercholesterolaemic apolipoprotein E-deficient mice with angiotensin II infusion. In this aneurysm model as well, aortic expressions of an adhesion molecule, a macrophage marker, and inflammatory factors were suppressed with the inhibited expression and activity of matrix metalloproteinases in the aorta.ConclusionEndothelial NF-κB activation up-regulates adhesion molecule expression, which may trigger macrophage infiltration and inflammation in the adventitia and media. Thus, the endothelium plays important roles in vascular remodelling and aneurysm formation through its intracellular NF-κB signalling.

本文言語English
ページ(範囲)106-114
ページ数9
ジャーナルCardiovascular Research
97
1
DOI
出版ステータスPublished - 2013 1 1

ASJC Scopus subject areas

  • 生理学
  • 循環器および心血管医学
  • 生理学(医学)

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