高血糖条件下内皮微粒促进的血管重构抑制作用被消除。
Endothelial microparticle-promoted inhibition of vascular remodeling is abrogated under hyperglycaemic conditions.
机构信息
Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
出版信息
J Mol Cell Cardiol. 2017 Nov;112:91-94. doi: 10.1016/j.yjmcc.2017.09.004. Epub 2017 Sep 14.
BACKGROUND
Endothelial microparticles (EMPs) inhibit vascular remodeling by transferring functional microRNA (miRNA) into target vascular smooth muscle cells (VSMCs). Because EMPs are increased in diabetic patients and potentially linked to vascular complications in diabetes mellitus, we sought to determine whether effects of EMPs generated under high glucose concentration on vascular remodeling might differ from EMPs derived from untreated cells.
METHODS AND RESULTS
EMPs were generated from human coronary endothelial cells (HCAEC) exposed to high glucose concentrations in order to mimic diabetic conditions. These EMPs were defined as 'hyperglycaemic' EMPs (hgEMPs) and their miRNA transfer capacity and functional effects were compared with EMPs generated from 'healthy' untreated HCAECs. In vitro, the intercellular transfer of antiproliferative miRNA-126-3p from ECs to VSMCs via EMPs was significantly reduced under hyperglycaemic conditions. Additionally, EMP-mediated inhibition of the miRNA-126-3p target LRP6 and of VSMC migration and proliferation was abrogated, when hgEMPs were used. In vivo, the inhibitory effect of EMPs on neointima formation, VSMC proliferation and macrophage infiltration was abolished in mice treated with hgEMPs.
CONCLUSION
Pathological hyperglycaemic conditions weaken potentially protective intercellular communication mechanisms by affecting EMP content and function.
背景
内皮细胞来源的微囊泡（endothelial microparticles，EMPs）通过将功能性 microRNA（miRNA）转移至靶血管平滑肌细胞（vascular smooth muscle cells，VSMCs），从而抑制血管重构。由于糖尿病患者中 EMPs 水平升高，且与糖尿病血管并发症密切相关，因此我们试图确定高糖浓度下产生的 EMPs 对血管重构的影响是否与未经处理的细胞衍生的 EMPs 不同。
方法和结果
为模拟糖尿病状态，我们将人冠状动脉内皮细胞（human coronary endothelial cells，HCAEC）暴露于高葡萄糖浓度下以产生 EMPs。这些 EMPs 被定义为“高糖诱导的” EMPs（hyperglycaemic EMPs，hgEMPs），并比较了它们的 miRNA 转移能力和功能效应与来自“健康”未经处理的 HCAECs 的 EMPs。在体外，高糖条件下，ECs 通过 EMPs 向 VSMCs 转移的抗增殖 miRNA-126-3p 显著减少。此外，当使用 hgEMPs 时，EMP 介导的 miRNA-126-3p 靶基因 LRP6 以及 VSMC 迁移和增殖的抑制作用也被消除。在体内，用 hgEMPs 处理的小鼠中，EMP 对新生内膜形成、VSMC 增殖和巨噬细胞浸润的抑制作用被消除。
结论
高血糖病理条件通过影响 EMP 含量和功能，削弱了潜在的保护性细胞间通讯机制。
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