Department of Physiological Sciences, Stellenbosch University, Stellenbosch Private Bag X1, Stellenbosch, 7602, South Africa.
Central Analytical Facilities, Fluorescence Imaging Unit Stellenbosch University, Stellenbosch Private Bag X1, Stellenbosch, 7602, South Africa.
Cardiovasc Diabetol. 2018 Nov 2;17(1):141. doi: 10.1186/s12933-018-0783-z.
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.
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.
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.
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.
2 型糖尿病(T2DM)与心血管疾病(CVD)之间存在很强的相关性,CVD 和动脉粥样硬化的存在是糖尿病患者发病率和死亡率的主要原因。T2DM 伴有多种凝血异常,包括异常的血栓形成或淀粉样纤维蛋白(原)、失调的炎症分子的存在。血小板与血栓形成密切相关,特别容易受到炎症细胞因子的影响。
因此,本研究的目的是评估健康个体和糖尿病个体的全血(高)凝血性、血小板超微结构和受体表达以及白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和可溶性 P 选择素(sP-选择素)的水平。通过扫描电子显微镜(SEM)评估血小板形态,通过共聚焦显微镜和流式细胞术评估 GPIIb/IIIa 受体表达,并用 FITC-PAC-1 和 CD41-PE 抗体进行。使用多重分析评估 IL-1β、IL-6 和 IL-8 以及 sP-选择素的水平。
在 T2DM 中,循环炎症标志物、高凝和血小板激活显著上调,流式细胞术和共聚焦显微镜显示 GPIIb/IIIa 受体表达增加。分析表明,这些受体还被释放到微颗粒上,SEM 证实了这一点。
总之,这提供了机制证据,表明 T2DM 中血小板的病理状态和淀粉样纤维蛋白(原)可能是心血管事件风险增加的基础。