The Cardiovascular Effect of the Uremic Solute Indole-3 Acetic Acid - Aix-Marseille Université Accéder directement au contenu
Article Dans Une Revue Journal of the American Society of Nephrology Année : 2015

The Cardiovascular Effect of the Uremic Solute Indole-3 Acetic Acid

Résumé

In CKD, uremic solutes may induce endothelial dysfunction, inflammation, and oxidative stress, leading to increased cardiovascular risk. We investigated whether the uremic solute indole-3 acetic acid (IAA) predicts clinical outcomes in patients with CKD and has prooxidant and proinflammatory effects. We studied 120 patients with CKD. During the median study period of 966 days, 29 patients died and 35 experienced a major cardiovascular event. Kaplan-Meier analysis revealed that mortality and cardiovascular events were significantly higher in the higher IAA group (IAA>3.73 mu M) than in the lower IAA group (IAA<3.73 mu M). Multivariate Cox regression analysis demonstrated that serum IAA was a significant predictor of mortality and cardiovascular events after adjustments for age and sex; cholesterol, systolic BP, and smoking; C-reactive protein, phosphate, body mass index, and albumin; diastolic BP and history of cardiovascular disease; and uremic toxins p-cresyl sulfate and indoxyl sulfate. Notably, IAA level remained Predictive of mortality when adjusted for CKD stage. IAA levels were positively correlated with markers of inflammation and oxidative stress: C-reactive protein and malondialdehyde, respectively. In cultured human endothelial cells, IAA activated an inflammatory nongenomic aryl hydrocarbon receptor (AhR)/p38MAPK/NF-kappa B pathway that induced the proinflammatory enzyme cyclooxygenase-2. Additionally, IAA increased production of endothelial reactive oxygen species. In conclusion, serum IAA may be an independent predictor of mortality and cardiovascular events in patients with CKD. In vitro, IAA induces endothelial inflammation and oxidative stress and activates an inflammatory AhR/p38MAPK/NF-kappa B pathway.
Fichier principal
Vignette du fichier
Dou et al IAA CVD final manuscript 2 (1).pdf (798.3 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-01610425 , version 1 (16-05-2022)

Identifiants

Citer

Laetitia Dou, Marion Sallée, Claire Cerini, Stéphane Poitevin, Bertrand Gondouin, et al.. The Cardiovascular Effect of the Uremic Solute Indole-3 Acetic Acid. Journal of the American Society of Nephrology, 2015, 26 (4), pp.876-887. ⟨10.1681/ASN.2013121283⟩. ⟨hal-01610425⟩
64 Consultations
38 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More