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Article

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

by
Belal Chami
1,
Nicola Barrie
1,
Xiaoping Cai
1,
Xiaosuo Wang
1,
Moumita Paul
2,
Rebecca Morton-Chandra
2,
Alexandra Sharland
2,
Joanne M. Dennis
1,
Saul B. Freedman
3 and
Paul K. Witting
1,*
1
Discipline of Pathology, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, Australia
2
Transplantation Immunobiology Group, Central Clinical School, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, Australia
3
Sydney Medical School, the University of Sydney, ANZAC Research Institute, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2015, 16(5), 11101-11124; https://doi.org/10.3390/ijms160511101
Submission received: 19 February 2015 / Revised: 25 March 2015 / Accepted: 27 April 2015 / Published: 15 May 2015
(This article belongs to the Section Biochemistry)
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Abstract

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.
Keywords: serum amyloid A; inflammation; atherosclerosis; high-density lipoprotein serum amyloid A; inflammation; atherosclerosis; high-density lipoprotein
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MDPI and ACS Style

Chami, B.; Barrie, N.; Cai, X.; Wang, X.; Paul, M.; Morton-Chandra, R.; Sharland, A.; Dennis, J.M.; Freedman, S.B.; Witting, P.K. Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells. Int. J. Mol. Sci. 2015, 16, 11101-11124. https://doi.org/10.3390/ijms160511101

AMA Style

Chami B, Barrie N, Cai X, Wang X, Paul M, Morton-Chandra R, Sharland A, Dennis JM, Freedman SB, Witting PK. 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. 2015; 16(5):11101-11124. https://doi.org/10.3390/ijms160511101

Chicago/Turabian Style

Chami, Belal, Nicola Barrie, Xiaoping Cai, Xiaosuo Wang, Moumita Paul, Rebecca Morton-Chandra, Alexandra Sharland, Joanne M. Dennis, Saul B. Freedman, and Paul K. Witting. 2015. "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 16, no. 5: 11101-11124. https://doi.org/10.3390/ijms160511101

APA Style

Chami, B., Barrie, N., Cai, X., Wang, X., Paul, M., Morton-Chandra, R., Sharland, A., Dennis, J. M., Freedman, S. B., & Witting, P. K. (2015). 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, 16(5), 11101-11124. https://doi.org/10.3390/ijms160511101

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