Rosiglitazone attenuates indoxyl sulphate-induced endothelial dysfunction

Abstract

Indoxyl sulphate is a protein-bound uraemic toxin that has deleterious effects on the cardiovascular system. Rosiglitazone (RGZ) is an insulin sensitizer used for glycaemic control in type 2 diabetes. Rosiglitazone has been shown to be beneficial for cardiovascular disease because of its pleiotropic effects. Whether RGZ can improve indoxyl sulphate-induced endothelial damage has not been investigated. In the present in vitro study, we examined the effects of RGZ on indoxyl sulphate-induced endothelial injury. Endothelial cells were exposed to RGZ (5 and 10 μmol/L) and then treated with indoxyl sulphate (100 and 1000 μmol/L) for 48 h. Indoxyl sulphate upregulated intracellular cell adhesion molecule-1, vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 expression. Indoxyl sulphate also increased the abundance of NADPH oxidase 4 (NOX4) and nuclear factor (NF)-κB. Both extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) signalling pathways were activated after 48 h treatment with indoxyl sulphate. Pretreatment of cells with both concentrations of RGZ improved indices of endothelial injury. In addition, RGZ attenuated the increase in NOX4 and NF-κB and prevented the activation of the ERK1/2 and p38 MAPK signalling pathways. We conclude that RGZ ameliorates indoxyl sulphate-induced endothelial injury.

Keywords: endothelial dysfunction; indoxyl sulphate; rosiglitazone.