IKKbeta-dependent NF-kappaB pathway controls vascular inflammation and intimal hyperplasia

Nuclear factor-kappaB (NF-kappaB)-mediated vascular inflammation is a prominent characteristic of atherogenesis and restenosis. We noted that angioplastic injury to carotid artery elicited two phases of NF-kappaB activation characterized by an early activation in the arterial media and a late activa...

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Bibliographic Details
Published in:The FASEB journal 2005-08, Vol.19 (10), p.1293-1295
Main Authors: Bu, De-xiu, Erl, Wolfgang, de Martin, Rainer, Hansson, Göran K, Yan, Zhong-qun
Format: Article
Language:English
Subjects:
Angioplasty - adverse effects
Animals
Apoptosis
Carotid Arteries - pathology
Cell Proliferation
Hyperplasia
I-kappa B Kinase - physiology
Male
Medicin och hälsovetenskap
Muscle, Smooth, Vascular - pathology
NF-kappa B - physiology
Rats
Rats, Sprague-Dawley
Signal Transduction - physiology
Tunica Intima - pathology
Vasculitis - etiology
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Summary:Nuclear factor-kappaB (NF-kappaB)-mediated vascular inflammation is a prominent characteristic of atherogenesis and restenosis. We noted that angioplastic injury to carotid artery elicited two phases of NF-kappaB activation characterized by an early activation in the arterial media and a late activation coupled with high levels of inhibitor of IkappaB kinase (IKK) activity in intima. These findings prompted us to elucidate the role for the different phases of NF-kappaB activation and IKK in the progress of vascular repair. Our results show that blockade of the early NF-kappaB activation by perivascular administration of pyrrolidine dithiocarbamate transiently attenuates the expression of proinflammatory genes in the injured vessels but does not affect intimal formation. Interruption of IKKbeta by overexpressing a dominant-negative IKKbeta in the injured artery effectively inhibited the late phase of NF-kappaB activation, resulting in down-regulation of inducible nitric oxide synthase, tumor necrosis factor alpha, and monocyte chemoattractant protein-1 expression in conjunction with a 36% reduction in intima size, albeit with a lack of inhibitory effect on the early NF-kappaB activation. Collectively, these findings show that the IKKbeta-mediated late-phase NF-kappaB activation contributes to intimal hyperplasia and the accompanied vascular inflammatory responses.
ISSN:1530-6860
1530-6860
DOI:10.1096/fj.04-2645fje