The Aryl Hydrocarbon Receptor-Activating Effect of Uremic Toxins from Tryptophan Metabolism: A New Concept to Understand Cardiovascular Complications of Chronic Kidney Disease

Marion Sallée (1, 2) , Laetitia Dou (1) , Claire Cerini (1) , Stéphane Poitevin (1) , Philippe Brunet (2, 1) , Stéphane Burtey (1, 2)

1 VRCM - Vascular research center of Marseille
2 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]

Patients with chronic kidney disease (CKD) have a higher risk of cardiovascular diseases and suffer from accelerated atherosclerosis. CKD patients are permanently exposed to uremic toxins, making them good candidates as pathogenic agents. We focus here on uremic toxins from tryptophan metabolism because of their potential involvement in cardiovascular toxicity: indolic uremic toxins (indoxyl sulfate, indole-3 acetic acid, and indoxyl-beta-d-glucuronide) and uremic toxins from the kynurenine pathway (kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and quinolinic acid). Uremic toxins derived from tryptophan are endogenous ligands of the transcription factor aryl hydrocarbon receptor (AhR). AhR, also known as the dioxin receptor, interacts with various regulatory and signaling proteins, including protein kinases and phosphatases, and Nuclear Factor-Kappa-B. AhR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin and some polychlorinated biphenyls is associated with an increase in cardiovascular disease in humans and in mice. In addition, this AhR activation mediates cardiotoxicity, vascular inflammation, and a procoagulant and prooxidant phenotype of vascular cells. Uremic toxins derived from tryptophan have prooxidant, proinflammatory, procoagulant, and pro-apoptotic effects on cells involved in the cardiovascular system, and some of them are related with cardiovascular complications in CKD. We discuss here how the cardiovascular effects of these uremic toxins could be mediated by AhR activation, in a ``dioxin-like'' effect.

Mots clés: tryptophan-derived uremic toxins; aryl hydrocarbon receptor; chronic kidney disease; cardiovascular diseases

Domaines: Urologie et Néphrologie; Cardiologie et système cardiovasculaire; Biochimie, Biologie Moléculaire

Marion Sallée, Laetitia Dou, Claire Cerini, Stéphane Poitevin, Philippe Brunet, et al.. The Aryl Hydrocarbon Receptor-Activating Effect of Uremic Toxins from Tryptophan Metabolism: A New Concept to Understand Cardiovascular Complications of Chronic Kidney Disease. Toxins, 2014, 6 (3), pp.934-949. ⟨10.3390/toxins6030934⟩. ⟨hal-01610428⟩