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 |
Published version: | http://dx.doi.org/10.3390/ijms20010105 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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hdl_121454.pdf | Published version | 2.03 MB | Adobe PDF | View/Open |
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