AGE/RAGE 诱导通过 NOX 衍生的 ROS 途径释放 EMP。
AGE/RAGE-Induced EMP Release via the NOX-Derived ROS Pathway.
机构信息
Department of Endocrinology, East Hospital, Tongji University, Shanghai 200120, China.
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
出版信息
J Diabetes Res. 2018 Mar 18;2018:6823058. doi: 10.1155/2018/6823058. eCollection 2018.
OBJECTIVE
Diabetes is associated with accelerated formation of advanced glycation end products (AGEs) that are extensively found in circulating endothelial microparticles (EMPs). This study aimed to investigate whether AGEs have a direct effect on EMP formation and the possible underlying mechanism.
METHODS
In vitro, cultured human umbilical vein endothelial cells (HUVECs) were incubated with AGEs (200 and 400 g/ml) for 24 hours with or without pretreatment with anti-RAGE antibody, NOX inhibitor, or ROS scavenger. The number of CD31-positive EMPs was assessed by flow cytometry.
RESULTS
The number of EMPs was significantly increased in HUVECs stimulated by AGEs in a dose-dependent manner. In addition, receptors for AGEs (RAGE), NAD(P)H oxidase (NOX), and reactive oxygen species (ROS) were increased by AGEs as compared to the control group. These changes could be reversed when HUVECs were pretreated with anti-RAGE antibody. Moreover, inhibition of NOX as well as antioxidant treatment reduced the release of EMPs induced by AGEs.
CONCLUSION
Our study suggested that AGEs increased EMP generation, which was mediated by RAGE signaling through NOX-derived ROS.
目的
糖尿病与晚期糖基化终产物（AGEs）的形成加速有关，AGEs 广泛存在于循环内皮微颗粒（EMP）中。本研究旨在探讨 AGEs 是否对 EMP 的形成有直接影响，以及可能的潜在机制。
方法
在体外，培养的人脐静脉内皮细胞（HUVEC）用 AGEs（200 和 400μg/ml）孵育 24 小时，或用抗 RAGE 抗体、NOX 抑制剂或 ROS 清除剂预处理。通过流式细胞术评估 CD31 阳性 EMP 的数量。
结果
与对照组相比，AGEs 以剂量依赖的方式刺激 HUVEC 后，EMP 的数量明显增加。此外，与对照组相比，AGEs 还增加了 AGEs 的受体（RAGE）、NAD（P）H 氧化酶（NOX）和活性氧（ROS）。当 HUVEC 用抗 RAGE 抗体预处理时，这些变化可以逆转。此外，NOX 抑制和抗氧化剂治疗减少了 AGEs 诱导的 EMP 释放。
结论
我们的研究表明，AGEs 通过 RAGE 信号通过 NOX 衍生的 ROS 增加了 EMP 的产生。
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