Microparticles from Hyperphosphatemia-Stimulated Endothelial Cells Promote Vascular Calcification Through Astrocyte-Elevated Gene-1
Microparticles from Hyperphosphatemia-Stimulated Endothelial Cells Promote Vascular Calcification Through Astrocyte-Elevated Gene-1
复制标题
来自高磷血症刺激的内皮细胞的微粒通过星形胶质细胞升高的基因 1 促进血管钙化
DOI：
10.1007/s00223-022-00960-6
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发表时间：
2022-02-23
影响因子：
4.2
通讯作者：
He, Zhangxiu
中科院分区：
文献类型：
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作者：
Xiang, Yazhou;Duan, Yingjie;He, Zhangxiu
内皮微粒（EMP）可在慢性肾病（CKD）中释放。高无机磷酸盐（HP）的血浆浓度被认为是CKD患者血管钙化的决定性因素。因此，我们探讨了HP诱导的EMPs（HP-EMPs）在血管钙化中的作用及其可能机制。我们观察到血管平滑肌细胞（VSMCs）捕获的HP-EMPs的形状动态变化，从罕见的点状、圆形到圆形或圆形。结果表明，HP-EMPs可直接促进VSMC钙化，或通过信号转导和转录激活因子3（STAT 3）/骨形态发生蛋白2（BMP 2）信号通路加速HP诱导的VSMC钙化。AEG-1活性增加，通过HP-EMPs诱导VSMC钙化，从尿毒症大鼠动脉，或从尿毒症大鼠治疗HP-EMPs。AEG-1缺乏会阻止VSMC的钙沉积，而AEG-1过表达会加剧VSMC的钙沉积。agomiR-153- 3 p可抑制miR-153 - 3 p的靶点AEG-1。值得注意的是，通过尾静脉注射适体-agomiR-153 - 3 p对miR-153 - 3 p的VSMC特异性增强减少了用HP-EMP治疗或未治疗的两种尿毒症大鼠中的钙沉积。HP-EMPs可直接诱导VSMCs钙化并加速Pi诱导的钙化，AEG-1可能是HP-EMPs诱导VSMCs钙化的重要调节因子。这项研究揭示了影响HP-EMP产生或AEG-1活性的治疗药物，这可能有利于治疗血管钙化。
Endothelial microparticles (EMPs) can be released in chronic kidney disease (CKD). Plasma concentration of high inorganic phosphate (HP) is considered as a decisive determinant of vascular calcification in CKD. We therefore explored the role of HP-induced EMPs (HP-EMPs) in the vascular calcification and its potential mechanism. We observed the shape of HP-EMPs captured by vascular smooth muscle cells (VSMCs) dynamically changed from rare dots, rosettes, to semicircle or circle. Our results demonstrated that HP-EMPs could directly promote VSMC calcification, or accelerate HP-induced calcification through signal transducers and activators of transcription 3 (STAT3)/bone morphogenetic protein-2 (BMP2) signaling pathway. AEG-1 activity was increased through HP-EMPs-induced VSMC calcification, in arteries from uremic rats, or from uremic rats treated with HP-EMPs. AEG-1 deficiency blocked, whereas AEG-1 overexpression exacerbated, the calcium deposition of VSMCs. AEG-1, a target of miR-153-3p, could be suppressed by agomiR-153-3p. Notably, VSMC-specific enhance of miR-153-3p by tail vein injection of aptamer-agomiR-153-3p decreased calcium deposition in both uremia rats treated with HP-EMPs or not. HP-EMPs could directly induce VSMCs calcification and accelerate Pi-induced calcification, and AEG-1 may act as crucial regulator of HP-EMPs-induced vascular calcification. This study sheds light on the therapeutic agents that influence HP-EMPs production or AEG-1 activity, which may be of benefit to treat vascular calcification.