不同糖耐量患者循环微颗粒的水平和特征。
Circulating levels and characterization of microparticles in patients with different degrees of glucose tolerance.
机构信息
Department of Medicine-DIMED, University of Padova, Padua, Italy.
Department of Chemical Sciences, University of Padova, Padua, Italy.
出版信息
Cardiovasc Diabetol. 2017 Sep 19;16(1):118. doi: 10.1186/s12933-017-0600-0.
BACKGROUND
Microparticles (MPs) are vesicular structures shed from endothelial or circulating blood cells, after activation or apoptosis, and can be considered markers of vascular damage. We aimed to determine the levels of circulating MPs, their content of miRNA-126-3p and 5p, and their relationship with early endothelial activation/damage, in patients with different degree of glucose tolerance.
METHODS
CD62E, CD62P, CD142, CD45 circulating MPs, their apoptotic (AnnexinV) fractions, and miRNA-126 expression were determined in 39 prediabetic (PreDM), 68 type 2 diabetic (T2DM), and 53 control (NGT) subjects, along with main anthropometric and biochemical measurements. MPs were analysed by flow cytometry. miRNA-126 was measured by quantitative real-time PCR. Plasma antioxidant capacity was determined by electronic spin resonance; ICAM-1, and VCAM-1 by ELISA.
RESULTS
Activated endothelial cell-derived MPs (CD62E) were significantly increased in PreDM and T2DM in comparison to NGT (p < 0.0001). AnnexinV/CD62E MPs and Annexin V MPs were significantly increased in T2DM compared to PreDM and NGT (p < 0.001); other MPs were not significantly different among groups. Plasma antioxidant capacity was significantly decreased in PreDM and T2DM compared to NGT (p = 0.001); VCAM-1 significantly increased in PreDM and T2DM in comparison to NGT (p = 0.001). miR-126-3p expression, but not miR-126-5p, in MPs, decreased significantly and progressively from NGT, to PreDM, and T2DM (p < 0.001). In PreDM and T2DM, CD62E MPs level was significantly and negatively associated with plasma glucose (p = 0.004).
CONCLUSION
We show for the first time that circulating CD62E MPs level and miR-126-3p content in MPs are abnormal in subjects with pre-diabetes; the content of miR-126-3p correlates with markers of endothelial inflammation, such as VCAM-1, plasma antioxidant capacity, and microparticles, well-accepted markers of endothelial dysfunction.
背景
微粒（MPs）是内皮细胞或循环血细胞在激活或凋亡后释放的囊泡结构，可以被视为血管损伤的标志物。我们旨在确定不同程度葡萄糖耐量患者循环 MPs 的水平、其 miRNA-126-3p 和 5p 的含量及其与早期内皮激活/损伤的关系。
方法
在 39 名糖尿病前期（PreDM）、68 名 2 型糖尿病（T2DM）和 53 名对照（NGT）患者中，测定 CD62E、CD62P、CD142、CD45 循环 MPs、其凋亡（AnnexinV）部分和 miRNA-126 的表达，并进行主要的人体测量和生化测量。通过流式细胞术分析 MPs。通过定量实时 PCR 测量 miRNA-126。通过电子自旋共振测定血浆抗氧化能力；通过 ELISA 测定 ICAM-1 和 VCAM-1。
结果
与 NGT 相比，PreDM 和 T2DM 中激活的内皮细胞衍生 MPs（CD62E）显著增加（p<0.0001）。与 PreDM 和 NGT 相比，T2DM 中 AnnexinV/CD62E MPs 和 Annexin V MPs 显著增加（p<0.001）；各组之间其他 MPs 无显著差异。与 NGT 相比，PreDM 和 T2DM 中的血浆抗氧化能力显著降低（p=0.001）；与 NGT 相比，PreDM 和 T2DM 中的 VCAM-1 显著增加（p=0.001）。MPs 中的 miR-126-3p 表达而非 miR-126-5p 表达，从 NGT、PreDM 和 T2DM 显著且逐渐降低（p<0.001）。在 PreDM 和 T2DM 中，CD62E MPs 水平与血浆葡萄糖显著负相关（p=0.004）。
结论
我们首次表明，糖尿病前期患者循环 CD62E MPs 水平和 MPs 中 miR-126-3p 含量异常；miR-126-3p 的含量与内皮炎症标志物（如 VCAM-1、血浆抗氧化能力和公认的内皮功能障碍标志物 MPs）相关。
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