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. / Dissertation (MSc (Physiology))--University of Pretoria, 2020. / NRF / Physiology / MSc (Physiology) / Unrestricted
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:up/oai:repository.up.ac.za:2263/79097 |
| Date | 15 December 2020 |
| Creators | Nxumalo, Mikateko |
| Contributors | Phulukdaree, Alisa, u14249996@tuks.co.za, Soma, Prashilla, Alummoottil, Sajee |
| Publisher | University of Pretoria |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Dissertation |
| Rights | © 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. |
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