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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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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