Investigating the amyloidogenic potential of serum amyloid a in type ii diabetes mellitus
| dc.contributor.advisor | Pretorius, Resia | en_ZA |
| dc.contributor.author | Thomson, Greig James Angus | en_ZA |
| dc.contributor.other | Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. | en_ZA |
| dc.date.accessioned | 2019-08-26T14:57:53Z | |
| dc.date.accessioned | 2019-12-11T06:59:58Z | |
| dc.date.available | 2019-08-26T14:57:53Z | |
| dc.date.available | 2019-12-11T06:59:58Z | |
| dc.date.issued | 2019-12 | |
| dc.description | Thesis (MSc)--Stellenbosch University, 2019. | en_ZA |
| dc.description.abstract | ENGLISH ABSTRACT: Introduction: Type II Diabetes Mellitus (T2DM) is a non-communicable disease associated with chronic low-grade inflammation and persistent activation of the acute phase response (APR). Serum amyloid A (SAA) is one of the proteins of the APR and has previously been shown to induce amyloidogensis in fibrin(ogen) ex vivo. The impact of SAA on the haematological and its amyloidogenic potential in T2DM has however yet to be determined. Further to this, literature has noted the ability of various molecules to “mop” and reverse fibrin amyloid formation, thus identification of a molecule able to “mop” SAA’s haematological impact would be highly beneficial in future. Aim: To quantify SAA levels in T2DM before determining the impact of this molecule on the haematological system. Further to this, determining the amyloidogenic potential of SAA in this disease state. Finally, the study aims at determining whether high-density lipoprotein (HDL), lipopolysaccharide-binding protein (LBP) or the combination of these two molecules are effective SAA mopping agents. Methods: The blood of 75 participants (n=36 control participants, n=39 T2DM participants) was collected and analysed for both quantitative and morphological markers. Quantitative markers include: inflammatory biomarker profiling and thromboelastography whereas the morphological markers include: whole blood scanning electron microscopy, fibrin clot scanning electron microscopy and fibrin clot confocal microscopy. Additionally, a control study was performed where SAA, HDL and LBP were incubated in the whole blood ex vivo before being analysed for these measurable and morphological markers. Lastly, an experimental study was performed whereby the efficiency of the mopping agents was tested ex vivo in T2DM whole blood. Results: SAA was found to be significantly elevated (p < 0.0001), 10-fold, in T2DM and induced platelet hyperactivation and agglutination. Furthermore, this study confirms that SAA is indeed amyloidogenic in nature. Qualitative SEM fibrin analysis showed that SAA induced the formation of dense matted amyloid deposits in the fibrin fibres. This was confirmed quantitatively when confocal microscopy, using amyloid specific stains, showed SAA induced a significant (p = 0.0452 and p = 0.0062) increase in amyloid signal in two of the three fluorescent markers. HDL and LBP proved to be ineffective SAA mopping agents. Conclusion: SAA is indeed amyloidogenic in nature and is contributing to the abnormal fibrin formation observed in T2DM. Despite this however, T2DM is a complex disease whereby various molecules and physiological mechanisms are altered. Thus, attributing the numerous haematological changes to a singular molecule is unfitting. Consequently, the use of a single molecule targeting “mopping” agent to reverse or inhibit these haematological alterations seems impractical. | en_ZA |
| dc.description.version | Masters | en_ZA |
| dc.format.extent | xi, 108 pages : illustrations | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/10019.1/107337 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | |
| dc.rights.holder | Stellenbosch University | |
| dc.subject | Serum amyloid A | en_ZA |
| dc.subject | Diabetes -- Treatment | en_ZA |
| dc.subject | Blood --Examination | en_ZA |
| dc.subject | Amyloidosis -- Physiological effect | en_ZA |
| dc.subject | High density lipoproteins | en_ZA |
| dc.subject | Fibrin -- Analysis | en_ZA |
| dc.subject | Acute phase response | en_ZA |
| dc.subject | UCTD | en_ZA |
| dc.title | Investigating the amyloidogenic potential of serum amyloid a in type ii diabetes mellitus | en_ZA |
| dc.type | Thesis | en_ZA |