Abstract
Complex associations exist between inflammation and thrombosis, with the inflammatory state tending to promote coagulation. Fibrinogen, an acute phase protein, has been shown to interact with the amyloidogenic ß-amyloid protein of Alzheimer’s disease. However, little is known about the association between fibrinogen and serum amyloid A (SAA), a highly fibrillogenic protein that is one of the most dramatically changing acute phase reactants in the circulation. To study the role of SAA in coagulation and thrombosis, in vitro experiments were performed where purified human SAA, in concentrations resembling a modest acute phase response, was added to platelet-poor plasma (PPP) and whole blood (WB), as well as purified and fluorescently labelled fibrinogen. Results from thromboelastography (TEG) suggest that SAA causes atypical coagulation with a fibrin(ogen)-mediated increase in coagulation, but a decreased platelet/fibrin(ogen) interaction. In WB scanning electron microscopy analysis, SAA mediated red blood cell (RBC) agglutination, platelet activation and clumping, but not platelet spreading. Following clot formation in PPP, the presence of SAA increased amyloid formation of fibrin(ogen) as determined both with auto-fluorescence and with fluorogenic amyloid markers, under confocal microcopy. SAA also binds to fibrinogen, as determined with a fluorescent-labelled SAA antibody and correlative light electron microscopy (CLEM). The data presented here indicate that SAA can affect coagulation by inducing amyloid formation in fibrin(ogen), as well as by propelling platelets to a more prothrombotic state. The discovery of these multiple and complex effects of SAA on coagulation invite further mechanistic analyses.
Document Type
Article
Publication Date
2-28-2019
Digital Object Identifier (DOI)
https://doi.org/10.1038/s41598-019-39056-x
Funding Information
We thank the Biotechnology and Biological Sciences Research Council (grant BB/L025752/1) as well as the National Research Foundation (NRF) of South Africa (91548: Competitive Program) and the Medical Research Council of South Africa (MRC) (Self-Initiated Research Program) for supporting this collaboration.
Repository Citation
Page, Martin J.; Thomson, Greig J. A.; Nunes, J. Massimo; Engelbrecht, Anna-Mart; Nell, Theo A.; de Villiers, Willem J. S.; de Beer, Maria C.; Engelbrecht, Lize; Kell, Douglas B.; and Pretorius, Etheresia, "Serum Amyloid A Binds to Gibrin(ogen), Promoting Fibrin Amyloid Formation" (2019). Physiology Faculty Publications. 144.
https://uknowledge.uky.edu/physiology_facpub/144
Notes/Citation Information
Published in Scientific Reports, v. 9, article no. 3102, p. 1-14.
© The Author(s) 2019
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.