Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/121454
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Type: Journal article
Title: NFκB inhibition mitigates serum amyloid a-induced pro-atherogenic responses in endothelial cells and leukocyte adhesion and adverse changes to endothelium function in isolated aorta
Other Titles: NFkappaB inhibition mitigates serum amyloid a-induced pro-atherogenic responses in endothelial cells and leukocyte adhesion and adverse changes to endothelium function in isolated aorta
Author: Vallejo, A.
Chami, B.
Dennis, J.M.
Simone, M.
Ahmad, G.
Abdo, A.I.
Sharma, A.
Shihata, W.A.
Martin, N.
Chin-Dusting, J.P.F.
de Haan, J.B.
Witting, P.K.
Citation: International Journal of Molecular Sciences, 2019; 20(1):18-18
Publisher: MDPI
Issue Date: 2019
ISSN: 1661-6596
1422-0067
Statement of
Responsibility: 
Abigail Vallejo, Belal Chami, Joanne M. Dennis, Martin Simone, Gulfam Ahmad, Adrian I. Abdo ... et al.
Abstract: The acute phase protein serum amyloid A (SAA) is associated with endothelial dysfunction and early-stage atherogenesis. Stimulation of vascular cells with SAA increases gene expression of pro-inflammation cytokines and tissue factor (TF). Activation of the transcription factor, nuclear factor kappa-B (NFκB), may be central to SAA-mediated endothelial cell inflammation, dysfunction and pro-thrombotic responses, while targeting NFκB with a pharmacologic inhibitor, BAY11-7082, may mitigate SAA activity. Human carotid artery endothelial cells (HCtAEC) were pre-incubated (1.5 h) with 10 μM BAY11-7082 or vehicle (control) followed by SAA (10 μg/mL; 4.5 h). Under these conditions gene expression for TF and Tumor Necrosis Factor (TNF) increased in SAA-treated HCtAEC and pre-treatment with BAY11-7082 significantly (TNF) and marginally (TF) reduced mRNA expression. Intracellular TNF and interleukin 6 (IL-6) protein also increased in HCtAEC supplemented with SAA and this expression was inhibited by BAY11-7082. Supplemented BAY11-7082 also significantly decreased SAA-mediated leukocyte adhesion to apolipoprotein E-deficient mouse aorta in ex vivo vascular flow studies. In vascular function studies, isolated aortic rings pre-treated with BAY11-7082 prior to incubation with SAA showed improved endothelium-dependent vasorelaxation and increased vascular cyclic guanosine monophosphate (cGMP) content. Together these data suggest that inhibition of NFκB activation may protect endothelial function by inhibiting the pro-inflammatory and pro-thrombotic activities of SAA.
Keywords: Nuclear; transcription; endothelium; atherosclerosis; serum amyloid A; aorta
Rights: © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
DOI: 10.3390/ijms20010105
Grant ID: http://purl.org/au-research/grants/arc/DP160102063
http://purl.org/au-research/grants/nhmrc/1125392
Appears in Collections:Aurora harvest 4
Medicine publications

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