International Journal of Molecular Sciences | |
Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells | |
Belal Chami3  Nicola Barrie3  Xiaoping Cai3  Xiaosuo Wang3  Moumita Paul2  Rebecca Morton-Chandra2  Alexandra Sharland2  Joanne M. Dennis3  Saul B. Freedman1  Paul K. Witting3  | |
[1] Sydney Medical School, the University of Sydney, ANZAC Research Institute, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia; E-Mail:;Transplantation Immunobiology Group, Central Clinical School, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, Australia; E-Mails:;Discipline of Pathology, Sydney Medical School, the University of Sydney, Sydney, NSW 2006, Australia; E-Mails: | |
关键词: serum amyloid A; inflammation; atherosclerosis; high-density lipoprotein; | |
DOI : 10.3390/ijms160511101 | |
来源: mdpi | |
【 摘 要 】
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.
【 授权许可】
CC BY
© 2015 by the authors; licensee MDPI, Basel, Switzerland.
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