Plasma Exosomes Derived From Patients With End-Stage Renal Disease and Renal Transplant Recipients Have Different Effects on Vascular Calcification

Xiao Lin; Ting Zhu; Feng Xu; Jia-Yu Zhong; Fuxingzi Li; Su-Kang Shan; Feng Wu; Bei Guo; Ming-Hui Zheng; Yi Wang; Qiu-Shuang Xu; Xiao-Bo Liao; Hong-Yu Lu; Xu-Biao Xie; Ling-Qing Yuan

doi:10.3389/fcell.2020.618228

Plasma Exosomes Derived From Patients With End-Stage Renal Disease and Renal Transplant Recipients Have Different Effects on Vascular Calcification

Front Cell Dev Biol. 2021 Jan 28:8:618228. doi: 10.3389/fcell.2020.618228. eCollection 2020.

Authors

Xiao Lin^{1

2}, Ting Zhu^{2

3}, Feng Xu², Jia-Yu Zhong⁴, Fuxingzi Li², Su-Kang Shan², Feng Wu⁵, Bei Guo², Ming-Hui Zheng², Yi Wang², Qiu-Shuang Xu², Xiao-Bo Liao⁶, Hong-Yu Lu⁷, Xu-Biao Xie⁸, Ling-Qing Yuan²

Affiliations

¹ Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China.
² Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China.
³ Department of Endocrinology, Central Hospital of Yiyang, Yiyang, China.
⁴ Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, China.
⁵ Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, China.
⁶ Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
⁷ Xiangya Medical College, Central South University, Changsha, China.
⁸ Department of Kidney Transplantation, The Second Xiangya Hospital, Central South University, Changsha, China.

Abstract

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.

Keywords: Annexin-A2; ESRD; Fetuin-A; MGP; exosomes; vascular calcification.