title: 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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang-Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chia-An
authors.initials: CA
authors.lastname: Chou
authors.forename: Hwee-Yeong
authors.initials: HY
authors.lastname: Ng
authors.forename: Wei-Hung
authors.initials: WH
authors.lastname: Kuo
authors.forename: Ting-Yu Terry
authors.initials: TY
authors.lastname: Chiou
authors.forename: Sung-Nan
authors.initials: SN
authors.lastname: Pei
authors.forename: Lung-Chih
authors.initials: LC
authors.lastname: Li
authors.forename: Yueh-Ting
authors.initials: YT
authors.lastname: Lee
authors.forename: Chien-Te
authors.initials: CT
authors.lastname: Lee
mesh_terms: D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007200:Indican / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D020928:Mitogen-Activated Protein Kinases; D007200:Indican
keywords: endothelial dysfunction; indoxyl sulphate; rosiglitazone