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The association of methylglyoxal-adducts with kinetics and ultrastructure of fibrin clots in coronary artery disease patients with type 2 diabetes mellitus
Dissertation (MSc (Physiology))--University of Pretoria, 2020.
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University of Pretoria
2021
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| _version_ | 1867613702075711488 |
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| access_status_str | Open Access |
| author2 | Phulukdaree, Alisa |
| author_browse | Phulukdaree, Alisa |
| author_facet | Phulukdaree, Alisa |
| collection | Thesis |
| dc_rights_str_mv | © 2019 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Dissertation (MSc (Physiology))--University of Pretoria, 2020. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/79097 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:40:20.497Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/79097 The association of methylglyoxal-adducts with kinetics and ultrastructure of fibrin clots in coronary artery disease patients with type 2 diabetes mellitus Phulukdaree, Alisa u14249996@tuks.co.za Soma, Prashilla Alummoottil, Sajee Nxumalo, Mikateko Methylglyoxal-adducts Fibrin clots Coronary artery disease Type 2 diabetes mellitus (T2DM) UCTD Health sciences theses SDG-03 Health sciences theses SDG-17 Dissertation (MSc (Physiology))--University of Pretoria, 2020. Background: Glycation influences the ultrastructure and clot kinetics of fibrin clots due to the post-translational modifications in fibrinogen. Methylglyoxal (MG) is used to measure the level of glycation which has been associated with the pathogenesis of type 2 diabetes Melilites (T2DM) and coronary heart disease (CHD). The aim of the study was to determine the role of MG on clot kinetics and fibrin clot structure in CHD patients with and without T2DM to provide insight into the mechanism of pathogenesis of atherosclerosis in T2DM which results in the development of CHD. Methodology: Scanning electron microscopy (SEM) was used to evaluate the morphology of fibrin clots. Thromboelastography (TEG) was used to assess the physiological clot properties (kinetics). Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of methylglyoxal-adducts. Results: The morphology of clots from controls analysed using SEM showed thick and thin fibres which created an organised mesh of fibrin fibres. In T2DM, CHD with T2DM and CHD some alterations in the morphology were observed. The ultrastructure micrographs in CHD shows that some of the fibrin fibres formed have individual fibres with both thick and thin fibres as well as a thick mass of fibres with a net-like structure that forms dense-matted deposits. In addition, the fibrin fibres are not organised. The densitometry analysis between controls and patient groups’ (CHD: mean (standard deviation) 0.42±0.11; CHD+T2DM: 0.31±0.08 and T2DM: 0.29±0.08) was found to be significantly lower in all groups compared to the control which had a mean of 0.57±0.1, p<0.0001. There are no significant differences in the alpha angle between CHD, T2DM, CHD with T2DM and controls (60.88±2.321˚ vs. 60.81±2.385˚ vs. 59.09± 3.185˚ vs. 66.47±1.300˚, p=0.5279). There was no significant difference found in the K-value between T2DM, CHD with T2DM, CHD and control subjects (3.458±0.446mins vs. 5.118±1.589mins vs. 3.758±0.450mins vs. 2.839±0.2156mins, p=0.0102). The maximum amplitude was higher in T2DM patients compared to CHD, CHD with T2DM and controls (40.51±1.914mm vs. 34.10±2.127mm vs. 33.12±3.365mm vs. 33.60±1.525mm, p=0.0102). The MRTG was higher in CHD compared to T2DM, CHD 4 with T2DM and controls (10.74±3.335 dyn cm-2 s -1 vs. 4.268±0.690 dyn cm-2 s -1 vs. 5.046± 0.927 dyn cm-2 s -1 vs. 6.535±0.664 dyn cm-2 s -1 , p=0.0096). The reaction time was higher in CHD with T2DM patients compared to T2DM, CHD and controls (32.58±4.005min vs. 23.92±2.793min vs. 21.29± 2.383min vs. 8.322±0.886min, p<0.0001). There was no significant difference found in the TTG between T2DM, CHD with T2DM, CHD and control subjects (231.3±28.68 dyn cm-2 vs. 258.5±38.15 dyn cm2 vs. 343.7±71.92 dyn cm-2 vs. 287.7±21.37 dyn cm-2 , p=0.8421). The TMRTG was higher in T2DM patients compared to T2DM, CHD with T2DM, CHD and controls (23.91±2.409mins vs. 20.46±3.411mins vs. 14.14±1.287mins vs. 10.16±0.751mins, p<0.0001). To assess if an association between MG-adducts and clot kinetics exists, the Spearman r correlation was completed for each clot parameter. The reaction time (p=0.0047, 95% CI: 0.138 to 0.665) and time taken before maximum speed of the clot growth to be achieved (p=0.3958, 95% CI: 0.072 to 0.644) was significant. This indicates the relationship between the parameters i.e., the higher the level of MGadducts present, the longer it takes for clotting to begin and reach maximum speed of formation. Conclusion: This study showed that there are ultrastructural differences in fibrin fibres formed in CHD patients with T2DM. The viscoelastic parameters indicated that haemostasis was irregular in CHD and T2DM. The levels of MG-adducts were much higher in T2DM, CHD with T2DM and CHD and may be a contributing factor to the pathogenesis associated with altered coagulation in these patients. NRF em2026 Physiology MSc (Physiology) Unrestricted SDG-03: Good health and well-being SDG-17: Partnerships for the goals 2021-03-25T08:08:32Z 2021-03-25T08:08:32Z 2021-12-16 2020-12-15 Dissertation Nxumalo, M 2020, The association of methylglyoxal-adducts with kinetics and ultrastructure of fibrin clots in coronary artery disease patients with type 2 diabetes mellitus, MSc (Physiology) Dissertation, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/79097> A2021 http://hdl.handle.net/2263/79097 en © 2019 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | Methylglyoxal-adducts Fibrin clots Coronary artery disease Type 2 diabetes mellitus (T2DM) UCTD Health sciences theses SDG-03 Health sciences theses SDG-17 The association of methylglyoxal-adducts with kinetics and ultrastructure of fibrin clots in coronary artery disease patients with type 2 diabetes mellitus |
| title | The association of methylglyoxal-adducts with kinetics and ultrastructure of fibrin clots in coronary artery disease patients with type 2 diabetes mellitus |
| title_full | The association of methylglyoxal-adducts with kinetics and ultrastructure of fibrin clots in coronary artery disease patients with type 2 diabetes mellitus |
| title_fullStr | The association of methylglyoxal-adducts with kinetics and ultrastructure of fibrin clots in coronary artery disease patients with type 2 diabetes mellitus |
| title_full_unstemmed | The association of methylglyoxal-adducts with kinetics and ultrastructure of fibrin clots in coronary artery disease patients with type 2 diabetes mellitus |
| title_short | The association of methylglyoxal-adducts with kinetics and ultrastructure of fibrin clots in coronary artery disease patients with type 2 diabetes mellitus |
| title_sort | association of methylglyoxal adducts with kinetics and ultrastructure of fibrin clots in coronary artery disease patients with type 2 diabetes mellitus |
| topic | Methylglyoxal-adducts Fibrin clots Coronary artery disease Type 2 diabetes mellitus (T2DM) UCTD Health sciences theses SDG-03 Health sciences theses SDG-17 |
| url | http://hdl.handle.net/2263/79097 |