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Platelet activity and hypercoagulation in type 2 diabetes
Authors:Lesha Pretorius  Greig J A Thomson  Rozanne C M Adams  Theo A Nell  Willem A Laubscher  Etheresia Pretorius
Institution:1.Department of Physiological Sciences,Stellenbosch University,Stellenbosch,South Africa;2.Central Analytical Facilities,Fluorescence Imaging Unit Stellenbosch University,Stellenbosch,South Africa;3.Department of Electronic and Electric Engineering, Faculty of Engineering,Stellenbosch University,Stellenbosch,South Africa
Abstract:

Background

A strong correlation exists between type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), with CVD and the presence of atherosclerosis being the prevailing cause of morbidity and mortality in diabetic populations. T2DM is accompanied by various coagulopathies, including anomalous clot formation or amyloid fibrin(ogen), the presence of dysregulated inflammatory molecules. Platelets are intimately involved in thrombus formation and particularly vulnerable to inflammatory cytokines.

Methods

The aim of this current study was therefore to assess whole blood (hyper)coagulability, platelet ultrastructure and receptor expression, as well as the levels of IL-1β, IL-6, IL-8 and sP-selectin in healthy and diabetic individuals. Platelet morphology was assessed through scanning electron microscopy (SEM), while assessment of GPIIb/IIIa receptor expression was performed with confocal microscopy and flow cytometry with the addition of FITC-PAC-1 and CD41-PE antibodies. IL-1β, IL-6 and IL-8 and sP-selectin levels were assessed using a multiplex assay.

Results

In T2DM there is significant upregulation of circulating inflammatory markers, hypercoagulation and platelet activation, with increased GPIIb/IIIa receptor expression, as seen with flow cytometry and confocal microscopy. Analyses showed that these receptors were additionally shed onto microparticles, which was confirmed with SEM.

Conclusions

Cumulatively, this provides mechanistic evidence that pathological states of platelets together with amyloid fibrin(ogen) in T2DM, might underpin an increased risk for cardiovascular events.
Keywords:
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