Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells

Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells

The acute phase protein serum amyloid A (SAA), a marker of inflammation, induces expression of pro-inflammatory and pro-thrombotic mediators including ICAM-1, VCAM-1, IL-6, IL-8, MCP-1 and tissue factor (TF) in both monocytes/macrophages and endothelial cells, and induces endothelial dysfunction—a p...

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Main Authors: Belal Chami, Nicola Barrie, Xiaoping Cai, Xiaosuo Wang, Moumita Paul, Rebecca Morton-Chandra, Alexandra Sharland, Joanne M. Dennis, Saul B. Freedman, Paul K. Witting
Format: Article
Language:English
Published: MDPI AG 2015-05-01
Series:International Journal of Molecular Sciences
Subjects:
serum amyloid A
inflammation
atherosclerosis
high-density lipoprotein
Online Access:http://www.mdpi.com/1422-0067/16/5/11101
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spelling doaj-3f492455b5f448c6978cf7abe45d48b62020-11-25T01:29:27ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-05-01165111011112410.3390/ijms160511101ijms160511101Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial CellsBelal Chami0Nicola Barrie1Xiaoping Cai2Xiaosuo Wang3Moumita Paul4Rebecca Morton-Chandra5Alexandra Sharland6Joanne M. Dennis7Saul B. Freedman8Paul K. Witting9Discipline of Pathology, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, AustraliaDiscipline of Pathology, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, AustraliaDiscipline of Pathology, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, AustraliaDiscipline of Pathology, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, AustraliaTransplantation Immunobiology Group, Central Clinical School, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, AustraliaTransplantation Immunobiology Group, Central Clinical School, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, AustraliaTransplantation Immunobiology Group, Central Clinical School, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, AustraliaDiscipline of Pathology, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, AustraliaSydney Medical School, the University of Sydney, ANZAC Research Institute, Concord Repatriation General Hospital, Sydney, NSW 2139, AustraliaDiscipline of Pathology, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, AustraliaThe acute phase protein serum amyloid A (SAA), a marker of inflammation, induces expression of pro-inflammatory and pro-thrombotic mediators including ICAM-1, VCAM-1, IL-6, IL-8, MCP-1 and tissue factor (TF) in both monocytes/macrophages and endothelial cells, and induces endothelial dysfunction—a precursor to atherosclerosis. In this study, we determined the effect of pharmacological inhibition of known SAA receptors on pro-inflammatory and pro-thrombotic activities of SAA in human carotid artery endothelial cells (HCtAEC). HCtAEC were pre-treated with inhibitors of formyl peptide receptor-like-1 (FPRL-1), WRW4; receptor for advanced glycation-endproducts (RAGE), (endogenous secretory RAGE; esRAGE) and toll-like receptors-2/4 (TLR2/4) (OxPapC), before stimulation by added SAA. Inhibitor activity was also compared to high-density lipoprotein (HDL), a known inhibitor of SAA-induced effects on endothelial cells. SAA significantly increased gene expression of TF, NFκB and TNF and protein levels of TF and VEGF in HCtAEC. These effects were inhibited to variable extents by WRW4, esRAGE and OxPapC either alone or in combination, suggesting involvement of endothelial cell SAA receptors in pro-atherogenic gene expression. In contrast, HDL consistently showed the greatest inhibitory action, and often abrogated SAA-mediated responses. Increasing HDL levels relative to circulating free SAA may prevent SAA-mediated endothelial dysfunction and ameliorate atherogenesis.http://www.mdpi.com/1422-0067/16/5/11101serum amyloid Ainflammationatherosclerosishigh-density lipoprotein
collection DOAJ
language English
format Article
sources DOAJ
author Belal Chami
Nicola Barrie
Xiaoping Cai
Xiaosuo Wang
Moumita Paul
Rebecca Morton-Chandra
Alexandra Sharland
Joanne M. Dennis
Saul B. Freedman
Paul K. Witting
spellingShingle Belal Chami
Nicola Barrie
Xiaoping Cai
Xiaosuo Wang
Moumita Paul
Rebecca Morton-Chandra
Alexandra Sharland
Joanne M. Dennis
Saul B. Freedman
Paul K. Witting
Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells
International Journal of Molecular Sciences
serum amyloid A
inflammation
atherosclerosis
high-density lipoprotein
author_facet Belal Chami
Nicola Barrie
Xiaoping Cai
Xiaosuo Wang
Moumita Paul
Rebecca Morton-Chandra
Alexandra Sharland
Joanne M. Dennis
Saul B. Freedman
Paul K. Witting
author_sort Belal Chami
title Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells
title_short Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells
title_full Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells
title_fullStr Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells
title_full_unstemmed Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells
title_sort serum amyloid a receptor blockade and incorporation into high-density lipoprotein modulates its pro-inflammatory and pro-thrombotic activities on vascular endothelial cells
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1422-0067
publishDate 2015-05-01
description The acute phase protein serum amyloid A (SAA), a marker of inflammation, induces expression of pro-inflammatory and pro-thrombotic mediators including ICAM-1, VCAM-1, IL-6, IL-8, MCP-1 and tissue factor (TF) in both monocytes/macrophages and endothelial cells, and induces endothelial dysfunction—a precursor to atherosclerosis. In this study, we determined the effect of pharmacological inhibition of known SAA receptors on pro-inflammatory and pro-thrombotic activities of SAA in human carotid artery endothelial cells (HCtAEC). HCtAEC were pre-treated with inhibitors of formyl peptide receptor-like-1 (FPRL-1), WRW4; receptor for advanced glycation-endproducts (RAGE), (endogenous secretory RAGE; esRAGE) and toll-like receptors-2/4 (TLR2/4) (OxPapC), before stimulation by added SAA. Inhibitor activity was also compared to high-density lipoprotein (HDL), a known inhibitor of SAA-induced effects on endothelial cells. SAA significantly increased gene expression of TF, NFκB and TNF and protein levels of TF and VEGF in HCtAEC. These effects were inhibited to variable extents by WRW4, esRAGE and OxPapC either alone or in combination, suggesting involvement of endothelial cell SAA receptors in pro-atherogenic gene expression. In contrast, HDL consistently showed the greatest inhibitory action, and often abrogated SAA-mediated responses. Increasing HDL levels relative to circulating free SAA may prevent SAA-mediated endothelial dysfunction and ameliorate atherogenesis.
topic serum amyloid A
inflammation
atherosclerosis
high-density lipoprotein
url http://www.mdpi.com/1422-0067/16/5/11101
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