Importance of endothelial NF-κB signalling in vascular remodelling and aortic aneurysm formation.
Cardiovasc Res
; 97(1): 106-14, 2013 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-23015640
ABSTRACT
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 ANDRESULTS:
To 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.CONCLUSION:
Endothelial 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aorta Abdominal
/
Endotélio Vascular
/
Transdução de Sinais
/
NF-kappa B
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Aneurisma da Aorta Abdominal
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Mediadores da Inflamação
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Artéria Femoral
/
Lesões do Sistema Vascular
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Cardiovasc Res
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Japão