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.
Highlights
Vascular calcification is mainly characterized as the medial of aortic calcification, and it often happens in patients with chronic kidney disease (CKD), especially end-stage renal disease (ESRD) (Nitta and Ogawa, 2015; Rangaswami et al, 2019)
The mechanism study found that Fetuin-A and matrix gla protein (MGP) were decreased, but Annexin-A2 was increased in the plasma exosomes derived from ESRD patients (ESRD-Ex)
We found that the content of plasma exosomes Fetuin-A and MGP was negatively while that of Annexin-A2 was positively correlated to calcification scores (CACS)
Summary
Vascular calcification is mainly characterized as the medial of aortic calcification (termed as Mönckeberg’s calcification), and it often happens in patients with chronic kidney disease (CKD), especially end-stage renal disease (ESRD) (Nitta and Ogawa, 2015; Rangaswami et al, 2019). Exosomes (Ex) are of endosomal origin from multivesicular bodies. They have a diameter of 30–100 nm, and they are released into the extracellular matrix. Numerous studies have reported that exosomes are usually regarded as mediator of cell-to-cell communication in physiological and pathological conditions because of their variety and the abundance of specific cargos, including proteins, lipids, and nucleic acids Li et al reported that exosomes derived from high-glucose-induced endothelial cells could carry versican protein to accelerate VSMCs calcification (Lin et al, 2019c). The role and mechanisms of exosomes in regulating vascular calcification in patients with ESRD is not very clear
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