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患有无症状动脉粥样硬化的糖尿病患者循环微颗粒的模式

The pattern of circulating microparticles in patients with diabetes mellitus with asymptomatic atherosclerosis.

作者信息

Berezin Alexander E, Kremzer Alexander A, Berezina Tatyana A, Martovitskaya Yu V

机构信息

a Internal Medicine Department , State Medical University , 26, Mayakovsky av., Zaporozhye 69035 , Ukraine.

b Clinical Pharmacology Department , State Medical University , Zaporozhye , Ukraine.

出版信息

Acta Clin Belg. 2016 Feb;71(1):38-45. doi: 10.1080/17843286.2015.1110894. Epub 2016 Feb 3.

Abstract

BACKGROUND

Accelerating atherosclerosis in type 2 diabetes mellitus (T2DM) patients may relate to imbalance between pattern of microparticles (MPs), which are frequently involved in repair of vasculature, tissue injury, inflammation and thrombosis. The aim of the study was to investigate the pattern of circulating MPs in T2DM patients with asymptomatic atherosclerosis.

METHODS

A total of 103 patients with T2DM (54 subjects without documented coronary atherosclerosis and 49 patients with angiographic evidence of asymptomatic coronary atherosclerosis) who were underwent a contrast-enhanced multispiral computed tomography angiography and 35 healthy volunteers were enrolled in the study. To determine circulating biomarkers, blood samples were collected at baseline. MPs were labelled and characterized by flow cytometry.

RESULTS

There were no significant differences between healthy volunteers and T2DM patients in circulating numbers of MPs labelled as CD41a+, CD64+, CD144+, CD144+/CD31+, Annexin V+, CD144+/annexin V+ and CD144+/CD31+/annexin V+. However, lower number of MPs with immune phenotypes CD62E+, CD105E+ and higher numbers of CD31+/annexin V+ MPs were reported in T2DM patients when compared with healthy volunteers. Therefore, we found an increased level of circulating CD41a+ MPs, CD144+/CD31+ MPs, CD31+/annexin V+ MPs, and decreased level of CD62E+ MPs in T2DM patients with asymptomatic coronary atherosclerosis in comparison with those who had no asymptomatic atherosclerosis. Using multivariate log regression analysis, BMI (odds ratio [OR] = 1.04, p = 0.001), LDL-C (OR = 1.05, p = 0.046), hs-CRP (OR = 1.07, p = 0.044), osteoprotegerin (OR = 1.07, p = 0.026), CD62E+ MPs (OR = 1.07, p = 0.001) and CD31+/annexin V+ MPs (OR = 1.12, p = 0.003) were determined independent predictive factors of asymptomatic atherosclerosis in T2DM patients.

CONCLUSION

Circulating levels of MP originated from apoptotic endothelial cell-derived were significantly increased in diabetic patients as compared with normal subjects, but level of activated endothelial cell-derived MPs was lower than in healthy volunteers. Among T2DM patients, an increased level of CD31+/annexin V+ MPs and decreased CD62E+ MPs were significantly associated with asymptomatic atherosclerosis.

摘要

背景

2型糖尿病(T2DM)患者动脉粥样硬化加速可能与微粒(MPs)模式失衡有关,MPs常参与血管修复、组织损伤、炎症和血栓形成。本研究旨在调查无症状动脉粥样硬化的T2DM患者循环MPs的模式。

方法

本研究纳入了103例T2DM患者(54例无冠状动脉粥样硬化记录的受试者和49例有冠状动脉造影无症状粥样硬化证据的患者),这些患者均接受了对比增强多层螺旋计算机断层血管造影,同时纳入了35名健康志愿者。为了确定循环生物标志物,在基线时采集血样。通过流式细胞术对MPs进行标记和表征。

结果

在标记为CD41a +、CD64 +、CD144 +、CD144 + / CD31 +、膜联蛋白V +、CD144 + /膜联蛋白V +和CD144 + / CD31 + /膜联蛋白V +的MPs循环数量方面,健康志愿者和T2DM患者之间无显著差异。然而,与健康志愿者相比,T2DM患者中具有免疫表型CD62E +、CD105E +的MPs数量较低,而CD31 + /膜联蛋白V + MPs数量较高。因此,我们发现与无无症状动脉粥样硬化的患者相比,无症状冠状动脉粥样硬化的T2DM患者循环中CD41a + MPs、CD144 + / CD31 + MPs、CD31 + /膜联蛋白V + MPs水平升高,而CD62E + MPs水平降低。使用多变量对数回归分析,确定BMI(比值比[OR]=1.04,p = 0.001)、低密度脂蛋白胆固醇(LDL-C,OR = 1.05,p = 0.046)、高敏C反应蛋白(hs-CRP,OR = 1.07,p = 0.044)、骨保护素(OR = 1.07,p = 0.026)、CD62E + MPs(OR = 1.07,p = 0.001)和CD31 + /膜联蛋白V + MPs(OR = 1.12,p = 0.003)是T2DM患者无症状动脉粥样硬化的独立预测因素。

结论

与正常受试者相比,糖尿病患者中源自凋亡内皮细胞的MPs循环水平显著升高,但活化内皮细胞衍生的MPs水平低于健康志愿者。在T2DM患者中,CD31 + /膜联蛋白V + MPs水平升高和CD62E + MPs水平降低与无症状动脉粥样硬化显著相关。

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