Page, Martin J, Thomson, Greig JA, Nunes, J Massimo, Engelbrecht, Anna-Mart, Nell, Theo A, de Villiers, Willem JS, de Beer, Maria C, Engelbrecht, Lize, Kell, Douglas B 
ORCID: 0000-0001-5838-7963 and Pretorius, Etheresia
(2019)
Serum amyloid A binds to fibrin(ogen), promoting fibrin amyloid formation.
SCIENTIFIC REPORTS, 9 (1).
3102-.
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Blood Platelets, Humans, Alzheimer Disease, Thrombosis, Acute-Phase Reaction, Amyloid, Serum Amyloid A Protein, Fibrinogen, Agglutination, Protein Binding, Blood Coagulation, Platelet Activation, Platelet Aggregation, Adult, Middle Aged, Female |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 25 Mar 2019 15:18 |
| Last Modified: | 19 Jan 2023 00:56 |
| DOI: | 10.1038/s41598-019-39056-x |
| Open Access URL: | https://doi.org/10.1038/s41598-019-39056-x |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3034888 |
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