Plasma Exosomes Derived From Patients With End-Stage Renal Disease and Renal Transplant Recipients Have Different Effects on Vascular Calcification.
Plasma Exosomes Derived From Patients With End-Stage Renal Disease and Renal Transplant Recipients Have Different Effects on Vascular Calcification.
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终末期肾病患者和肾移植受者的血浆外泌体对血管钙化有不同的影响
DOI：
10.3389/fcell.2020.618228
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发表时间：
2020
影响因子：
5.5
通讯作者：
Yuan LQ
中科院分区：
文献类型：
--
作者：
Lin X;Zhu T;Xu F;Zhong JY;Li F;Shan SK;Wu F;Guo B;Zheng MH;Wang Y;Xu QS;Liao XB;Lu HY;Xie XB;Yuan LQ
终末期肾病(ESRD)患者常发生广泛的进行性血管钙化，其过程中涉及多种钙化抑制物和促钙化因子。然而，终末期肾病患者血管钙化的机制仍不清楚。在本研究中，我们发现来自ESRD患者的血浆Exosome(ESRD-Ex)显著促进血管平滑肌细胞(VSMCs)的钙化，而来自肾移植受者的血浆Exosome(RTR-Ex)可以部分地抑制VSMCs的钙化。此外，ESRD-Ex的蛋白浓度显著高于正常健康对照组(NOR-Ex)和RTR-Ex，而钙化抑制因子基质玻璃蛋白(MGP)和胎球蛋白-A的含量显著低于Nor-Ex。钙化促进剂Annexin-A2在ESRD-Ex和RTR-Ex中的含量显著高于Nor-Ex。骨形态发生蛋白-2和核因子受体激活剂-κB配体在三组间差异无统计学意义。此外，RTR-Ex的胎球蛋白-A含量高于ESRD-Ex，但仍低于Nor-Ex。此外，血浆外切体中胎球蛋白-A和MGP水平均呈负相关，而血浆外切体中Annexin-A2水平与冠状动脉钙化积分(CACs)呈正相关。这些结果表明，ESRD-Ex可显著促进VSMCs的钙化，而肾移植可部分减弱外体的前钙化作用。ESRD-Ex胎球蛋白-A和MGP降低，Annexin-A2升高，肾移植可使胎球蛋白-A升高，而不是MGP。
End-stage renal disease (ESRD) patients usually develop extensive and progressive vascular calcification, and lots of calcification inhibitors as well as procalcifying factors are involved in the process. However, the mechanisms of vascular calcification in ESRD patients are still ill-defined. In the present study, we found that the plasma exosomes derived from ESRD patients (ESRD-Ex) promoted calcification of vascular smooth muscle cells (VSMCs) significantly, while plasma exosomes from renal transplant recipients (RTR-Ex) could partially attenuate VSMCs calcification. Moreover, the protein concentration of ESRD-Ex was significantly higher than plasma exosomes from the normal health control group (Nor-Ex) and RTR-Ex, and the content of both matrix gla protein (MGP) and Fetuin-A, the calcification inhibitors, were prominently lower in ESRD-Ex than those in Nor-Ex. The content of Annexin-A2, one of the calcification promoters, was significantly higher in ESRD-Ex and RTR-Ex than that in Nor-Ex. However, bone morphogenetic protein (BMP-2) and receptor activator for nuclear factor-κB ligand (Rankl) had no significant difference among the three groups. In addition, the content of Fetuin-A in RTR-Ex was higher than that in ESRD-Ex, although it was still lower than that in Nor-Ex. Furthermore, the levels of both Fetuin-A and MGP in plasma exosomes were negatively while the levels of Annexin-A2 in plasma exosomes was positively correlated to coronary artery calcification scores (CACS). These results indicated that ESRD-Ex significantly promoted VSMCs calcification, while renal transplantation could partially attenuate the procalcification effect of exosomes. Fetuin-A and MGP were decreased, but Annexin-A2 was increased in ESRD-Ex, and renal transplantation could increase the level of Fetuin-A rather than MGP.
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影响因子：
9.3
作者：
Leopold JA
通讯作者：
Leopold JA
影响因子：
24
作者：
Chen J;Budoff MJ;Reilly MP;Yang W;Rosas SE;Rahman M;Zhang X;Roy JA;Lustigova E;Nessel L;Ford V;Raj D;Porter AC;Soliman EZ;Wright JT Jr;Wolf M;He J;CRIC Investigators
通讯作者：
CRIC Investigators
DOI：
10.2215/cjn.05450513
发表时间：
2014-04-07
影响因子：
9.8
作者：
Scialla, Julia J.;Kao, W. H. Linda;Parekh, Rulan S.
通讯作者：
Parekh, Rulan S.
影响因子：
19.6
作者：
Chen, N. X.;Duan, D.;Moe, S. M.
通讯作者：
Moe, S. M.
影响因子：
6.2
作者：
Chen, Neal X.;O'Neill, Kalisha D.;Moe, Sharon M.
通讯作者：
Moe, Sharon M.