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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

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-...

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Autores principales: Vallejo, Abigail, Chami, Belal, Dennis, Joanne M., Simone, Martin, Ahmad, Gulfam, Abdo, Adrian I., Sharma, Arpeeta, Shihata, Waled A., Martin, Nathan, Chin-Dusting, Jaye P. F., de Haan, Judy B., Witting, Paul K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337750/
https://www.ncbi.nlm.nih.gov/pubmed/30597899
http://dx.doi.org/10.3390/ijms20010105
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author Vallejo, Abigail
Chami, Belal
Dennis, Joanne M.
Simone, Martin
Ahmad, Gulfam
Abdo, Adrian I.
Sharma, Arpeeta
Shihata, Waled A.
Martin, Nathan
Chin-Dusting, Jaye P. F.
de Haan, Judy B.
Witting, Paul K.
author_facet Vallejo, Abigail
Chami, Belal
Dennis, Joanne M.
Simone, Martin
Ahmad, Gulfam
Abdo, Adrian I.
Sharma, Arpeeta
Shihata, Waled A.
Martin, Nathan
Chin-Dusting, Jaye P. F.
de Haan, Judy B.
Witting, Paul K.
author_sort Vallejo, Abigail
collection PubMed
description 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.
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spelling pubmed-63377502019-01-22 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 Vallejo, Abigail Chami, Belal Dennis, Joanne M. Simone, Martin Ahmad, Gulfam Abdo, Adrian I. Sharma, Arpeeta Shihata, Waled A. Martin, Nathan Chin-Dusting, Jaye P. F. de Haan, Judy B. Witting, Paul K. Int J Mol Sci Article 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. MDPI 2018-12-28 /pmc/articles/PMC6337750/ /pubmed/30597899 http://dx.doi.org/10.3390/ijms20010105 Text en © 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/).
spellingShingle Article
Vallejo, Abigail
Chami, Belal
Dennis, Joanne M.
Simone, Martin
Ahmad, Gulfam
Abdo, Adrian I.
Sharma, Arpeeta
Shihata, Waled A.
Martin, Nathan
Chin-Dusting, Jaye P. F.
de Haan, Judy B.
Witting, Paul K.
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337750/
https://www.ncbi.nlm.nih.gov/pubmed/30597899
http://dx.doi.org/10.3390/ijms20010105
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