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Uremic Toxins and Vascular Dysfunction
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How do Uremic Toxins Affect the Endothelium?

Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba 81531-980, Brazil
Internal Medicine Department, Division of Nephrology, Universidade Federal do Paraná, Curitiba 80060-900, Brazil
Author to whom correspondence should be addressed.
Toxins 2020, 12(6), 412;
Received: 27 May 2020 / Revised: 15 June 2020 / Accepted: 19 June 2020 / Published: 20 June 2020
Uremic toxins can induce endothelial dysfunction in patients with chronic kidney disease (CKD). Indeed, the structure of the endothelial monolayer is damaged in CKD, and studies have shown that the uremic toxins contribute to the loss of cell–cell junctions, increasing permeability. Membrane proteins, such as transporters and receptors, can mediate the interaction between uremic toxins and endothelial cells. In these cells, uremic toxins induce oxidative stress and activation of signaling pathways, including the aryl hydrocarbon receptor (AhR), nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) pathways. The activation of these pathways leads to overexpression of proinflammatory (e.g., monocyte chemoattractant protein-1, E-selectin) and prothrombotic (e.g., tissue factor) proteins. Uremic toxins also induce the formation of endothelial microparticles (EMPs), which can lead to the activation and dysfunction of other cells, and modulate the expression of microRNAs that have an important role in the regulation of cellular processes. The resulting endothelial dysfunction contributes to the pathogenesis of cardiovascular diseases, such as atherosclerosis and thrombotic events. Therefore, uremic toxins as well as the pathways they modulated may be potential targets for therapies in order to improve treatment for patients with CKD. View Full-Text
Keywords: uremic toxins; endothelium; endothelial dysfunction uremic toxins; endothelium; endothelial dysfunction
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MDPI and ACS Style

Cunha, R.S.; Santos, A.F.; Barreto, F.C.; Stinghen, A.E.M. How do Uremic Toxins Affect the Endothelium? Toxins 2020, 12, 412.

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