The role of lipoteichoic acid on amyloidogenesis and its effect on erythrocytes and platelets
| dc.contributor.advisor | Pretorius, Resia | |
| dc.contributor.author | Nkosi, Nondumiso Belvia | |
| dc.contributor.other | Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. | |
| dc.date.accessioned | 2019-08-08T09:42:29Z | |
| dc.date.accessioned | 2019-12-11T06:59:07Z | |
| dc.date.available | 2019-08-08T09:42:29Z | |
| dc.date.available | 2019-12-11T06:59:07Z | |
| dc.date.issued | 2019-12 | |
| dc.description | Thesis (MSc)--Stellenbosch University, 2019. | en_ZA |
| dc.description.abstract | ENGLISH ABSTRACT: Hypercoagulation and amyloidogenesis are commonly known as hallmarks for inflammation. Hypercoagulation and amyloidogenesis are linked to quite a few communicable and non-communicable ailments such as cancer, rheumatoid arthritis and several neuro-inflammatory conditions, like Parkinson’s and Alzheimer’s disease. Recently, it was discovered that adding low concentrations of bacterial components such as lipopolysaccharide (LPS) to platelet poor plasma (PPP) and whole blood (WB) brings about hypercoagulation and amyloidogenesis. The main protein that showed these structural changes, was soluble fibrinogen. Fibrinogen changes to insoluble fibrin, in the presence of thrombin during clot formation. Studies show that in the presence of specific plasma proteins and/or “mopping” agents, the presence hypercoagulation and amyloid might be removed or reduced. An example of such serum protein is the presence of LPS binding protein (LBP). In this thesis, the aim is to investigate the effects of bacterial component lipoteichoic acid (LTA) when directly added to healthy WB and fibrinogen and compare the clotting profiles and ultrastructure of these samples to that of Type two diabetes mellites (T2DM) PPP. Furthermore, this thesis aims to investigate the potential role of Apolipoprotein A-1 (ApoA1) as a mopping agent, by adding ApoA1 to healthy WB, fibrinogen and T2DM PPP. Here we suggest that ApoA1 may reduce hypercoagulation and amyloidogenesis in healthy WB and fibrinogen with added amyloid forming molecule, LTA and T2DM PPP. We hypothesis that by adding low concentrations of LTA (5ng/L) to healthy WB and fibrinogen, LTA will cause hyperactivation of platelets, eryptosis of red blood cells (RBC) and amyloidogenesis in fibrin(ogen) respectively. In addition to this, we hypothesis that by adding ApoA1 to WB and fibrinogen that has been spiked with LTA, ApoA1 will attenuate supposed hyperactivation, eryptosis and amyloidogenesis. Moreover, we hypothesise that by adding ApoA1 to T2DM PPP, it will decrease the coagulopathies and amyloid state typically associated with T2DM patients. Thromboelastography was used to assess clotting parameters of WB and Scanning electron microscopy (SEM) was used to view any ultrastructural changes on RBC and platelets before and after the addition of LTA and LTA with ApoA1 to healthy WB. Confocal microscopy was used to investigate whether amyloid protein formation occurred in fibrin(ogen) in the presence of LTA and if this amyloid was reduced when ApoA1 was added. For our T2DM control’s, SEM and Confocal were used to view the differences in the PPP clot formed before and after the addition of ApoA1. The results for WB from the healthy controls showed a trend towards hypercoagulation in the presence of LTA and a trend towards attenuation of hypercoagulation and amyloidogenesis in the presence of ApoA1. In the T2DM model, a significant change was observed between the naïve T2DM PPP and the ApoA1 treated T2DM PPP. These are significant findings because they provide an alternative novel approach to the formation of a hypercoagulable environment and amyloidogenesis and these findings can be advantageous in finding a potential treatment of chronic inflammatory conditions. | en_ZA |
| dc.description.version | Masters | |
| dc.format.extent | x, 111 pages : illustrations | |
| dc.identifier.uri | http://hdl.handle.net/10019.1/107322 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | |
| dc.rights.holder | Stellenbosch University | |
| dc.subject | Blood -- Coagulation | en_ZA |
| dc.subject | Hypercoagulation -- Fibrosis | en_ZA |
| dc.subject | Erythrocytes -- Metabolism | en_ZA |
| dc.subject | Confocal microscopy | en_ZA |
| dc.subject | Microbial polysaccharides -- Biotechnology | en_ZA |
| dc.subject | Endotoxins -- Analysis | en_ZA |
| dc.subject | Amyloidosis -- Metabolism -- Disorders | en_ZA |
| dc.subject | Inflammation -- Immunological aspects | en_ZA |
| dc.subject | Fibrin | en_ZA |
| dc.subject | Blood platelets -- Metabolism | en_ZA |
| dc.subject | UCTD | en_ZA |
| dc.title | The role of lipoteichoic acid on amyloidogenesis and its effect on erythrocytes and platelets | en_ZA |
| dc.type | Thesis | en_ZA |