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Review
. 2020 Dec 21;12(12):811.
doi: 10.3390/toxins12120811.

Effects of Chronic Kidney Disease and Uremic Toxins on Extracellular Vesicle Biology

Linda Yaker  1 , Saïd Kamel  1   2 , Jérôme Ausseil  3   4 , Agnès Boullier  1   2
Affiliations
Review

Effects of Chronic Kidney Disease and Uremic Toxins on Extracellular Vesicle Biology

Linda Yaker et al. Toxins (Basel). .

Abstract

Vascular calcification (VC) is a cardiovascular complication associated with a high mortality rate, especially in patients with diabetes, atherosclerosis or chronic kidney disease (CKD). In CKD patients, VC is associated with the accumulation of uremic toxins, such as indoxyl sulphate or inorganic phosphate, which can have a major impact in vascular remodeling. During VC, vascular smooth muscle cells (VSMCs) undergo an osteogenic switch and secrete extracellular vesicles (EVs) that are heterogeneous in terms of their origin and composition. Under physiological conditions, EVs are involved in cell-cell communication and the maintenance of cellular homeostasis. They contain high levels of calcification inhibitors, such as fetuin-A and matrix Gla protein. Under pathological conditions (and particularly in the presence of uremic toxins), the secreted EVs acquire a pro-calcifying profile and thereby act as nucleating foci for the crystallization of hydroxyapatite and the propagation of calcification. Here, we review the most recent findings on the EVs' pathophysiological role in VC, the impact of uremic toxins on EV biogenesis and functions, the use of EVs as diagnostic biomarkers and the EVs' therapeutic potential in CKD.

Keywords: chronic kidney disease; extracellular vesicles; uremic toxins; vascular calcification.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The classification of extracellular vesicles (EVs) as a function of their biogenesis.
Figure 2
Figure 2
Biological functions of EVs.
Figure 3
Figure 3
The role of EVs in vascular calcification. VSMCs: vascular smooth muscle cells.
See this image and copyright information in PMC

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